{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:19:32Z","timestamp":1790936372508,"version":"4.1.0"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["91753000"],"award-info":[{"award-number":["91753000"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Formaldehyde (FA) has long been considered as a toxin and carcinogen due to its damaging effects to biological macromolecules, but its beneficial roles have been increasingly appreciated lately. Real-time monitoring of this reactive molecule in living systems is highly desired in order to decipher its physiological and\/or pathological functions, but a genetically encoded FA sensor is currently lacking. We herein adopt a structure-based study of the underlying mechanism of the FA-responsive transcription factor HxlR from <jats:italic>Bacillus subtilis<\/jats:italic>, which shows that HxlR recognizes FA through an intra-helical cysteine-lysine crosslinking reaction at its N-terminal helix \u03b11, leading to conformational change and transcriptional activation. By leveraging this FA-induced intra-helical crosslinking and gain-of-function reorganization, we develop the genetically encoded, reaction-based FA sensor\u2014FAsor, allowing spatial-temporal visualization of FA in mammalian cells and mouse brain tissues.<\/jats:p>","DOI":"10.1038\/s41467-020-20754-4","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T11:06:41Z","timestamp":1611572801000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Genetically encoded formaldehyde sensors inspired by a protein intra-helical crosslinking reaction"],"prefix":"10.1038","volume":"12","author":[{"given":"Rongfeng","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaofeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3125-2716","authenticated-orcid":false,"given":"Jingyi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9166-9919","authenticated-orcid":false,"given":"Yulong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0402-7417","authenticated-orcid":false,"given":"Peng R.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"20754_CR1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.2174\/1389557033488187","volume":"3","author":"H Kalasz","year":"2003","unstructured":"Kalasz, H. Biological role of formaldehyde, and cycles related to methylation, demethylation, and formaldehyde production. Mini Rev. Med. Chem. 3, 175\u2013192 (2003).","journal-title":"Mini Rev. Med. Chem."},{"key":"20754_CR2","first-page":"Ra122","volume":"11","author":"F Boomsma","year":"2005","unstructured":"Boomsma, F., Hut, H., Bhaggoe, U., van der Houwen, A. & van den Meiracker, A. Semicarbazide-sensitive amine oxidase (SSAO): from cell to circulation. Med. Sci. Monit. 11, Ra122\u2013Ra126 (2005).","journal-title":"Med. Sci. Monit."},{"key":"20754_CR3","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.cbpa.2012.09.015","volume":"16","author":"LJ Walport","year":"2012","unstructured":"Walport, L. J., Hopkinson, R. J. & Schofield, C. J. Mechanisms of human histone and nucleic acid demethylases. Curr. Opin. Chem. Biol. 16, 525\u2013534 (2012).","journal-title":"Curr. Opin. Chem. Biol."},{"key":"20754_CR4","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/nature11368","volume":"489","author":"JI Garaycoechea","year":"2012","unstructured":"Garaycoechea, J. I. et al. Genotoxic consequences of endogenous aldehydes on mouse haematopoietic stem cell function. Nature 489, 571\u2013575 (2012).","journal-title":"Nature"},{"key":"20754_CR5","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.molcel.2015.08.020","volume":"60","author":"LB Pontel","year":"2015","unstructured":"Pontel, L. B. et al. Endogenous formaldehyde is a hematopoietic stem cell genotoxin and metabolic carcinogen. Mol. Cell 60, 177\u2013188 (2015).","journal-title":"Mol. Cell"},{"key":"20754_CR6","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.cell.2017.05.010","volume":"169","author":"SLW Tan","year":"2017","unstructured":"Tan, S. L. W. et al. A class of environmental and endogenous toxins induces BRCA2 haploinsufficiency and genome instability. Cell 169, 1105\u20131118 (2017).","journal-title":"Cell"},{"key":"20754_CR7","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/bms.1200090808","volume":"9","author":"HD Heck","year":"1982","unstructured":"Heck, H. D., White, E. L. & Casanovaschmitz, M. Determination of formaldehyde in biological tissues by gas-chromatography mass-spectrometry. Biomed. Mass Spectrom. 9, 347\u2013353 (1982).","journal-title":"Biomed. Mass Spectrom."},{"key":"20754_CR8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15298668591394275","volume":"46","author":"HD Heck","year":"1985","unstructured":"Heck, H. D. et al. Formaldehyde (CH2O) concentrations in the blood of humans and Fischer-344 rats exposed to CH2O under controlled conditions. Am. Ind. Hyg. Assoc. J. 46, 1\u20133 (1985).","journal-title":"Am. Ind. Hyg. Assoc. J."},{"key":"20754_CR9","doi-asserted-by":"crossref","first-page":"e10234","DOI":"10.1371\/journal.pone.0010234","volume":"5","author":"ZQ Tong","year":"2010","unstructured":"Tong, Z. Q. et al. Tumor tissue-derived formaldehyde and acidic microenvironment synergistically induce bone cancer pain. PLoS ONE 5, e10234 (2010).","journal-title":"PLoS ONE"},{"key":"20754_CR10","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/cpr.12132","volume":"47","author":"M Rizzi","year":"2014","unstructured":"Rizzi, M., Cravello, B. & Reno, F. Textile industry manufacturing by-products induce human melanoma cell proliferation via ERK1\/2 activation. Cell Proliferat. 47, 578\u2013586 (2014).","journal-title":"Cell Proliferat."},{"key":"20754_CR11","doi-asserted-by":"crossref","unstructured":"Rizzi, M., Cravello, B., Tonello, S. & Reno, F. Formaldehyde solutions in simulated sweat increase human melanoma but not normal human keratinocyte cells proliferation. Toxicol. In Vitro 37, 106\u2013112 (2016).","DOI":"10.1016\/j.tiv.2016.09.009"},{"key":"20754_CR12","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/nature23481","volume":"548","author":"G Burgos-Barragan","year":"2017","unstructured":"Burgos-Barragan, G. et al. Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism. Nature 548, 549\u2013554 (2017).","journal-title":"Nature"},{"key":"20754_CR13","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1271\/bbb.70.10","volume":"70","author":"N Kato","year":"2006","unstructured":"Kato, N., Yurimoto, H. & Thauer, R. K. The physiological role of the ribulose monophosphate pathway in bacteria and archaea. Biosci. Biotechnol. Biochem. 70, 10\u201321 (2006).","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"20754_CR14","doi-asserted-by":"crossref","first-page":"10720","DOI":"10.1021\/bi9929711","volume":"39","author":"PC Sanghani","year":"2000","unstructured":"Sanghani, P. C. et al. Kinetic mechanism of human glutathione-dependent formaldehyde dehydrogenase. Biochemistry 39, 10720\u201310729 (2000).","journal-title":"Biochemistry"},{"key":"20754_CR15","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0009-2797(00)00272-6","volume":"130","author":"S Teng","year":"2001","unstructured":"Teng, S. et al. The formaldehyde metabolic detoxification enzyme systems and molecular cytotoxic mechanism in isolated rat hepatocytes. Chem. Biol. Interact. 130, 285\u2013296 (2001).","journal-title":"Chem. Biol. Interact."},{"key":"20754_CR16","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1124\/dmd.30.1.69","volume":"30","author":"RS Wang","year":"2002","unstructured":"Wang, R. S., Nakajima, T., Kawamoto, T. & Honma, T. Effects of aldehyde dehydrogenase-2 genetic polymorphisms on metabolism of structurally different aldehydes in human liver. Drug Metab. Dispos. 30, 69\u201373 (2002).","journal-title":"Drug Metab. Dispos."},{"key":"20754_CR17","doi-asserted-by":"crossref","first-page":"10886","DOI":"10.1021\/jacs.5b05340","volume":"137","author":"TF Brewer","year":"2015","unstructured":"Brewer, T. F. & Chang, C. J. An Aza-cope reactivity-based fluorescent probe for imaging formaldehyde in living cells. J. Am. Chem. Soc. 137, 10886\u201310889 (2015).","journal-title":"J. Am. Chem. Soc."},{"key":"20754_CR18","doi-asserted-by":"crossref","first-page":"10890","DOI":"10.1021\/jacs.5b05339","volume":"137","author":"A Roth","year":"2015","unstructured":"Roth, A., Li, H., Anorma, C. & Chan, J. A reaction-based fluorescent probe for imaging of formaldehyde in living cells. J. Am. Chem. Soc. 137, 10890\u201310893 (2015).","journal-title":"J. Am. Chem. Soc."},{"key":"20754_CR19","doi-asserted-by":"crossref","first-page":"9582","DOI":"10.1039\/C6CC04254F","volume":"52","author":"L He","year":"2016","unstructured":"He, L. et al. An ultra-fast illuminating fluorescent probe for monitoring formaldehyde in living cells, shiitake mushrooms, and indoors. Chem. Commun. 52, 9582\u20139585 (2016).","journal-title":"Chem. Commun."},{"key":"20754_CR20","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.1002\/anie.201510373","volume":"55","author":"Y Tang","year":"2016","unstructured":"Tang, Y., Kong, X., Xu, A., Dong, B. & Lin, W. Development of a two-photon fluorescent probe for imaging of endogenous formaldehyde in living tissues. Angew. Chem. Int. Ed. 55, 3356\u20133359 (2016).","journal-title":"Angew. Chem. Int. Ed."},{"key":"20754_CR21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cbpa.2017.04.010","volume":"39","author":"KJ Bruemmer","year":"2017","unstructured":"Bruemmer, K. J., Brewer, T. F. & Chang, C. J. Fluorescent probes for imaging formaldehyde in biological systems. Curr. Opin. Chem. Biol. 39, 17\u201323 (2017).","journal-title":"Curr. Opin. Chem. Biol."},{"key":"20754_CR22","doi-asserted-by":"crossref","first-page":"4036","DOI":"10.1039\/C8CS00956B","volume":"48","author":"Y Tang","year":"2019","unstructured":"Tang, Y., Ma, Y., Yin, J. & Lin, W. Strategies for designing organic fluorescent probes for biological imaging of reactive carbonyl species. Chem. Soc. Rev. 48, 4036\u20134048 (2019).","journal-title":"Chem. Soc. Rev."},{"key":"20754_CR23","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1038\/nchembio.2417","volume":"13","author":"YC Fan","year":"2017","unstructured":"Fan, Y. C., Makar, M., Wang, M. X. & Ai, H. W. Monitoring thioredoxin redox with a genetically encoded red fluorescent biosensor. Nat. Chem. Biol. 13, 1045\u20131052 (2017).","journal-title":"Nat. Chem. Biol."},{"key":"20754_CR24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.mie.2017.01.019","volume":"589","author":"L Sanford","year":"2017","unstructured":"Sanford, L. & Palmer, A. Recent advances in development of genetically encoded fluorescent sensors. Method. Enzymol. 589, 1\u201349 (2017).","journal-title":"Method. Enzymol."},{"key":"20754_CR25","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.cell.2018.06.042","volume":"174","author":"FM Sun","year":"2018","unstructured":"Sun, F. M. et al. A genetically encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice. Cell 174, 481\u2013496 (2018).","journal-title":"Cell"},{"key":"20754_CR26","first-page":"257","volume":"7","author":"NH Chen","year":"2016","unstructured":"Chen, N. H., Djoko, K. Y., Veyrier, F. J. & McEwan, A. G. Formaldehyde stress responses in bacterial pathogens. Front. Microbiol. 7, 257 (2016).","journal-title":"Front. Microbiol."},{"key":"20754_CR27","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1111\/j.1365-2958.2005.04702.x","volume":"57","author":"H Yurimoto","year":"2005","unstructured":"Yurimoto, H. et al. HxlR, a member of the DUF24 protein family, is a DNA-binding protein that acts as a positive regulator of the formaldehyde-inducible hxlAB operon in Bacillus subtilis. Mol. Microbiol. 57, 511\u2013519 (2005).","journal-title":"Mol. Microbiol."},{"key":"20754_CR28","doi-asserted-by":"crossref","first-page":"4169","DOI":"10.1128\/JB.01887-05","volume":"188","author":"MY Galperin","year":"2006","unstructured":"Galperin, M. Y. Structural classification of bacterial response regulators: diversity of output domains and domain combinations. J. Bacteriol. 188, 4169\u20134182 (2006).","journal-title":"J. Bacteriol."},{"key":"20754_CR29","doi-asserted-by":"crossref","first-page":"19502","DOI":"10.1074\/jbc.M116.745174","volume":"291","author":"D Osman","year":"2016","unstructured":"Osman, D. et al. The effectors and sensory sites of formaldehyde-responsive regulator FrmR and metal-sensing variant. J. Biol. Chem. 291, 19502\u201319516 (2016).","journal-title":"J. Biol. Chem."},{"key":"20754_CR30","doi-asserted-by":"crossref","DOI":"10.1038\/srep38879","volume":"6","author":"KJ Denby","year":"2016","unstructured":"Denby, K. J. et al. The mechanism of a formaldehyde-sensing transcriptional regulator. Sci. Rep. 6, 38879 (2016).","journal-title":"Sci. Rep."},{"key":"20754_CR31","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0168-6445(03)00054-8","volume":"27","author":"LS Busenlehner","year":"2003","unstructured":"Busenlehner, L. S., Pennella, M. A. & Giedroc, D. P. The SmtB\/ArsR family of metalloregulatory transcriptional repressors: structural insights into prokaryotic metal resistance. FEMS Microbiol. Rev. 27, 131\u2013143 (2003).","journal-title":"FEMS Microbiol. Rev."},{"key":"20754_CR32","doi-asserted-by":"crossref","first-page":"4178","DOI":"10.1093\/nar\/gkr1316","volume":"40","author":"GJ Palm","year":"2012","unstructured":"Palm, G. J. et al. Structural insights into the redox-switch mechanism of the MarR\/DUF24-type regulator HypR. Nucleic Acids Res. 40, 4178\u20134192 (2012).","journal-title":"Nucleic Acids Res."},{"key":"20754_CR33","doi-asserted-by":"crossref","first-page":"5010","DOI":"10.1073\/pnas.1219446110","volume":"110","author":"QJ Ji","year":"2013","unstructured":"Ji, Q. J. et al. Molecular mechanism of quinone signaling mediated through S-quinonization of a YodB family repressor QsrR. Proc. Natl Acad. Sci. USA 110, 5010\u20135015 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"20754_CR34","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1111\/j.1365-2958.2008.06110.x","volume":"67","author":"M Leelakriangsak","year":"2008","unstructured":"Leelakriangsak, M. et al. Regulation of quinone detoxification by the thiol stress sensing DUF24\/MarR-like repressor, YodB in Bacillus subtilis. Mol. Microbiol. 67, 1108\u20131124 (2008).","journal-title":"Mol. Microbiol."},{"key":"20754_CR35","doi-asserted-by":"crossref","first-page":"3197","DOI":"10.1073\/pnas.051636098","volume":"98","author":"T Nagai","year":"2001","unstructured":"Nagai, T., Sawano, A., Park, E. S. & Miyawaki, A. Circularly permuted green fluorescent proteins engineered to sense Ca2+. Proc. Natl Acad. Sci. USA 98, 3197\u20133202 (2001).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"20754_CR36","doi-asserted-by":"crossref","first-page":"8027","DOI":"10.1039\/c3cc44534h","volume":"49","author":"QJ Ji","year":"2013","unstructured":"Ji, Q. J., Zhao, B. S. & He, C. A highly sensitive and genetically encoded fluorescent reporter for ratiometric monitoring of quinones in living cells. Chem. Commun. 49, 8027\u20138029 (2013).","journal-title":"Chem. Commun."},{"key":"20754_CR37","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nmeth.4306","volume":"14","author":"RK Tao","year":"2017","unstructured":"Tao, R. K. et al. Genetically encoded fluorescent sensors reveal dynamic regulation of NADPH metabolism. Nat. Methods 14, 720\u2013728 (2017).","journal-title":"Nat. Methods"},{"key":"20754_CR38","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1111\/j.1365-2958.2008.06568.x","volume":"71","author":"TT Nguyen","year":"2009","unstructured":"Nguyen, T. T. et al. Genome-wide responses to carbonyl electrophiles in Bacillus subtilis: control of the thiol-dependent formaldehyde dehydrogenase AdhA and cysteine proteinase YraA by the MerR-family regulator YraB (AdhR). Mol. Microbiol. 71, 876\u2013894 (2009).","journal-title":"Mol. Microbiol."},{"key":"20754_CR39","doi-asserted-by":"crossref","first-page":"5089","DOI":"10.1021\/ac500810r","volume":"86","author":"D Siegel","year":"2014","unstructured":"Siegel, D., Meinema, A. C., Permentier, H., Hopfgartner, G. & Bischoff, R. Integrated quantification and identification of aldehydes and ketones in biological samples. Anal. Chem. 86, 5089\u20135100 (2014).","journal-title":"Anal. Chem."},{"key":"20754_CR40","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1073\/pnas.90.4.1247","volume":"90","author":"WM Keung","year":"1993","unstructured":"Keung, W. M. & Vallee, B. L. Daidzin\u2014a potent, selective inhibitor of human mitochondrial aldehyde dehydrogenase. Proc. Natl Acad. Sci. USA 90, 1247\u20131251 (1993).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"20754_CR41","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-23371-w","volume":"8","author":"SD Barnett","year":"2018","unstructured":"Barnett, S. D., Smith, C. R., Ulrich, C. C., Baker, J. E. & Buxton, I. L. O. S-nitrosoglutathione reductase underlies the dysfunctional relaxation to nitric oxide in preterm labor. Sci. Rep. 8, 5614 (2018).","journal-title":"Sci. Rep."},{"key":"20754_CR42","doi-asserted-by":"crossref","unstructured":"Umansky, C. et al. Endogenous formaldehyde scavenges cellular glutathione resulting in cytotoxic redox disruption. https:\/\/www.biorxiv.org\/content\/10.1101\/2020.05.14.090738v1bioRxiv (2020).","DOI":"10.1101\/2020.05.14.090738"},{"key":"20754_CR43","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1021\/acs.chemrestox.5b00038","volume":"28","author":"CD Aluise","year":"2015","unstructured":"Aluise, C. D. et al. Site-specific, intramolecular cross-linking of Pin1 active site residues by the lipid electrophile 4-Oxo-2-nonenal. Chem. Res. Toxicol. 28, 817\u2013827 (2015).","journal-title":"Chem. Res. Toxicol."},{"key":"20754_CR44","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nchembio.2284","volume":"13","author":"MJC Long","year":"2017","unstructured":"Long, M. J. C. et al. Akt3 is a privileged first responder in isozyme-specific electrophile response. Nat. Chem. Biol. 13, 333\u2013338 (2017).","journal-title":"Nat. Chem. Biol."},{"key":"20754_CR45","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/s41586-018-0622-0","volume":"562","author":"MJ Bollong","year":"2018","unstructured":"Bollong, M. J. et al. A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling. Nature 562, 600\u2013604 (2018).","journal-title":"Nature"},{"key":"20754_CR46","doi-asserted-by":"crossref","first-page":"4464","DOI":"10.1021\/acs.chemrev.9b00066","volume":"119","author":"S Parvez","year":"2019","unstructured":"Parvez, S., Long, M. J. C., Poganik, J. R. & Aye, Y. Redox signaling by reactive electrophiles and oxidants. Chem. Rev. 119, 4464\u20134469 (2019).","journal-title":"Chem. Rev."},{"key":"20754_CR47","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s42004-020-0324-z","volume":"3","author":"M Pietzke","year":"2020","unstructured":"Pietzke, M. et al. Amino acid dependent formaldehyde metabolism in mammals. Commun. Chem. 3, 78 (2020).","journal-title":"Commun. Chem."},{"key":"20754_CR48","doi-asserted-by":"crossref","first-page":"3206","DOI":"10.1182\/blood-2013-06-507962","volume":"122","author":"A Hira","year":"2013","unstructured":"Hira, A. et al. Variant ALDH2 is associated with accelerated progression of bone marrow failure in Japanese Fanconi anemia patients. Blood 122, 3206\u20133209 (2013).","journal-title":"Blood"},{"key":"20754_CR49","volume":"21","author":"D Nie","year":"2020","unstructured":"Nie, D. et al. Comprehensive analysis on phenotype and genetic basis of Chinese Fanconi anemia patients: dismal outcomes call for nationwide studies. BMC Med. Genet. 21, 118 (2020).","journal-title":"BMC Med. Genet."},{"key":"20754_CR50","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nchembio.1380","volume":"10","author":"ZY Hao","year":"2014","unstructured":"Hao, Z. Y. et al. The multiple antibiotic resistance regulator MarR is a copper sensor in Escherichia coli. Nat. Chem. Biol. 10, 21\u201328 (2014).","journal-title":"Nat. Chem. Biol."},{"key":"20754_CR51","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nmeth.1318","volume":"6","author":"DG Gibson","year":"2009","unstructured":"Gibson, D. G. et al. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat. Methods 6, 343\u2013345 (2009).","journal-title":"Nat. Methods"},{"key":"20754_CR52","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nchembio.644","volume":"7","author":"M Zhang","year":"2011","unstructured":"Zhang, M. et al. A genetically incorporated crosslinker reveals chaperone cooperation in acid resistance. Nat. Chem. Biol. 7, 671\u2013677 (2011).","journal-title":"Nat. Chem. Biol."},{"key":"20754_CR53","doi-asserted-by":"publisher","DOI":"10.1007\/s41365-018-0398-9","volume":"29","author":"QS Wang","year":"2018","unstructured":"Wang, Q. S. et al. Upgrade of macromolecular crystallography beamline BL17U1 at SSRF. Nucl. Sci. Tech. 29, 68 https:\/\/doi.org\/10.1007\/s41365-018-0398-9 (2018).","journal-title":"Nucl. Sci. Tech"},{"key":"20754_CR54","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","volume":"276","author":"Z Otwinowski","year":"1997","unstructured":"Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Method Enzymol. 276, 307\u2013326 (1997).","journal-title":"Method Enzymol."},{"key":"20754_CR55","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1107\/S0907444906019949","volume":"62","author":"W Minor","year":"2006","unstructured":"Minor, W., Cymborowski, M., Otwinowski, Z. & Chruszcz, M. HKL-3000: the integration of data reduction and structure solution\u2014from diffraction images to an initial model in minutes. Acta Crystallogr. D. 62, 859\u2013866 (2006).","journal-title":"Acta Crystallogr. D."},{"key":"20754_CR56","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1107\/S0021889807021206","volume":"40","author":"AJ Mccoy","year":"2007","unstructured":"Mccoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658\u2013674 (2007).","journal-title":"J. Appl. Crystallogr."},{"key":"20754_CR57","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1107\/S0907444910045749","volume":"67","author":"MD Winn","year":"2011","unstructured":"Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D. 67, 235\u2013242 (2011).","journal-title":"Acta Crystallogr. D."},{"key":"20754_CR58","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1107\/S0907444996012255","volume":"53","author":"GN Murshudov","year":"1997","unstructured":"Murshudov, G. N., Vagin, A. A. & Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D. 53, 240\u2013255 (1997).","journal-title":"Acta Crystallogr. D."},{"key":"20754_CR59","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"PD Adams","year":"2010","unstructured":"Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D. 66, 213\u2013221 (2010).","journal-title":"Acta Crystallogr. D."},{"key":"20754_CR60","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D. 66, 486\u2013501 (2010).","journal-title":"Acta Crystallogr. D."},{"key":"20754_CR61","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pro.3330","volume":"27","author":"CJ Williams","year":"2018","unstructured":"Williams, C. J. et al. MolProbity: more and better reference data for improved all-atom structure validation. Protein Sci. 27, 293\u2013315 (2018).","journal-title":"Protein Sci."},{"key":"20754_CR62","doi-asserted-by":"crossref","first-page":"W636","DOI":"10.1093\/nar\/gkz268","volume":"47","author":"F Madeira","year":"2019","unstructured":"Madeira, F. et al. The EMBL-EBI search and sequence analysis tools APIs in 2019. Nucleic Acids Res. 47, W636\u2013W641 (2019).","journal-title":"Nucleic Acids Res."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-020-20754-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-020-20754-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-020-20754-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T10:19:27Z","timestamp":1669976367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-020-20754-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,25]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["20754"],"URL":"https:\/\/doi.org\/10.1038\/s41467-020-20754-4","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,25]]},"assertion":[{"value":"5 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"581"}}