{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:24:38Z","timestamp":1772252678332,"version":"3.50.1"},"reference-count":70,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gianesini Foundation Fellowship","award":["3rd Edition, to AF"],"award-info":[{"award-number":["3rd Edition, to AF"]}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["BTC-PID2019-109306RB-I100"],"award-info":[{"award-number":["BTC-PID2019-109306RB-I100"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["SAF2016-76678-C2-2-R"],"award-info":[{"award-number":["SAF2016-76678-C2-2-R"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["BFU2017-89707-P"],"award-info":[{"award-number":["BFU2017-89707-P"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Protein oligomerization is key to countless physiological processes, but also to abnormal amyloid conformations implicated in over 25 mortal human diseases. Human Angiogenin (h-ANG), a ribonuclease A family member, produces RNA fragments that regulate ribosome formation, the creation of new blood vessels and stress granule function. Too little h-ANG activity leads to abnormal protein oligomerization, resulting in Amyotrophic Lateral Sclerosis (ALS) or Parkinson\u2019s disease. While a score of disease linked h-ANG mutants has been studied by X-ray diffraction, some elude crystallization. There is also a debate regarding the structure that RNA fragments adopt after cleavage by h-ANG. Here, to better understand the beginning of the process that leads to aberrant protein oligomerization, the solution secondary structure and residue-level dynamics of WT h-ANG and two mutants i.e., H13A and R121C, are characterized by multidimensional heteronuclear NMR spectroscopy under near-physiological conditions. All three variants are found to adopt well folded and highly rigid structures in the solution, although the elements of secondary structure are somewhat shorter than those observed in crystallography studies. R121C alters the environment of nearby residues only. By contrast, the mutation H13A affects local residues as well as nearby active site residues K40 and H114. The conformation characterization by CD and 1D 1H NMR spectroscopies of tRNAAla before and after h-ANG cleavage reveals a retention of the duplex structure and little or no G-quadruplex formation.<\/jats:p>","DOI":"10.3390\/ijms22031439","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T05:16:28Z","timestamp":1612156588000},"page":"1439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["NMR Characterization of Angiogenin Variants and tRNAAla Products Impacting Aberrant Protein Oligomerization"],"prefix":"10.3390","volume":"22","author":[{"given":"Andrea","family":"Fagagnini","sequence":"first","affiliation":[{"name":"Dipartimento di Neuroscienze, Biomedicina e Movimento, Sezione di Chimica Biologica, Universit\u00e0 di Verona, Strada Le Grazie 8, I-37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1889-1713","authenticated-orcid":false,"given":"Miguel","family":"Garav\u00eds","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica F\u00edsica \u201cRocasolano\u201d, Consejo Superior de Investigaciones Cient\u00edficas, c\/Serrano 119, E-28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"G\u00f3mez-Pinto","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica F\u00edsica \u201cRocasolano\u201d, Consejo Superior de Investigaciones Cient\u00edficas, c\/Serrano 119, E-28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Fasoli","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Biomedicina e Movimento, Sezione di Chimica Biologica, Universit\u00e0 di Verona, Strada Le Grazie 8, I-37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3179-7158","authenticated-orcid":false,"given":"Giovanni","family":"Gotte","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Biomedicina e Movimento, Sezione di Chimica Biologica, Universit\u00e0 di Verona, Strada Le Grazie 8, I-37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4187-165X","authenticated-orcid":false,"given":"Douglas V.","family":"Laurents","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica F\u00edsica \u201cRocasolano\u201d, Consejo Superior de Investigaciones Cient\u00edficas, c\/Serrano 119, E-28006 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1212\/WNL.36.4.511","article-title":"Familial Adult Motor Neuron Disease: Amyotrophic Lateral Sclerosis","volume":"36","author":"Mulder","year":"1986","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"238","DOI":"10.3109\/17482968.2011.584629","article-title":"Keeping up with Genetic Discoveries in Amyotrophic Lateral Sclerosis: The ALSoD and ALSGene Databases","volume":"12","author":"Lill","year":"2011","journal-title":"Amyotroph. Lateral Scler."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1002\/humu.22157","article-title":"ALSoD: A User-Friendly Online Bioinformatics Tool for Amyotrophic Lateral Sclerosis Genetics","volume":"33","author":"Abel","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrneurol.2011.153","article-title":"Clinical Diagnosis and Management of Amyotrophic Lateral Sclerosis","volume":"7","author":"Hardiman","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/nrneurol.2011.152","article-title":"Molecular Pathways of Motor Neuron Injury in Amyotrophic Lateral Sclerosis","volume":"7","author":"Ferraiuolo","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrneurol.2011.150","article-title":"Clinical Genetics of Amyotrophic Lateral Sclerosis: What Do We Really Know?","volume":"7","author":"Andersen","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/978-1-4419-6448-9_2","article-title":"Amyotrophic Lateral Sclerosis","volume":"685","author":"Perry","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Le Gall, L., Anakor, E., Connolly, O., Vijayakumar, U.G., Duddy, W.J., and Duguez, S. (2020). Molecular and Cellular Mechanisms Affected in ALS. J. Pers. Med., 10.","DOI":"10.1186\/s13395-020-00238-1"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7113","DOI":"10.1074\/jbc.REV119.007944","article-title":"Phase Separation of RNA-Binding Proteins in Physiology and Disease: An Introduction to the JBC Reviews Thematic Series","volume":"294","author":"Shorter","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1111\/j.1471-4159.2009.06383.x","article-title":"TDP-43 Is Recruited to Stress Granules in Conditions of Oxidative Insult","volume":"111","author":"Colombrita","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/ng1742","article-title":"ANG Mutations Segregate with Familial and \u201csporadic\u201d Amyotrophic Lateral Sclerosis","volume":"38","author":"Greenway","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1006\/abbi.1994.1318","article-title":"Human Pancreatic-Type and Nonpancreatic-Type Ribonucleases: A Direct Side-by-Side Comparison of Their Catalytic Properties","volume":"312","author":"Sorrentino","year":"1994","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5486","DOI":"10.1021\/bi00341a031","article-title":"Amino Acid Sequence of Human Tumor Derived Angiogenin","volume":"24","author":"Strydom","year":"1985","journal-title":"Biochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5141","DOI":"10.1021\/bi00390a037","article-title":"Isolation of Angiogenin from Normal Human Plasma","volume":"26","author":"Shapiro","year":"1987","journal-title":"Biochemistry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0002-9378(97)70508-8","article-title":"Angiogenin: A Marker for Preterm Delivery in Midtrimester Amniotic Fluid","volume":"176","author":"Spong","year":"1997","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5480","DOI":"10.1021\/bi00341a030","article-title":"Isolation and Characterization of Angiogenin, an Angiogenic Protein from Human Carcinoma Cells","volume":"24","author":"Fett","year":"1985","journal-title":"Biochemistry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1038\/ncb1800","article-title":"Glioblastoma Microvesicles Transport RNA and Proteins That Promote Tumour Growth and Provide Diagnostic Biomarkers","volume":"10","author":"Skog","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1158\/0008-5472.CAN-04-2058","article-title":"Angiogenin Is Translocated to the Nucleus of HeLa Cells and Is Involved in Ribosomal RNA Transcription and Cell Proliferation","volume":"65","author":"Tsuji","year":"2005","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1002\/(SICI)1097-4644(20000301)76:3<452::AID-JCB12>3.0.CO;2-Z","article-title":"Human Angiogenin Is Rapidly Translocated to the Nucleus of Human Umbilical Vein Endothelial Cells and Binds to DNA","volume":"76","author":"Hu","year":"2000","journal-title":"J. Cell. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1083\/jcb.200811106","article-title":"Angiogenin Cleaves TRNA and Promotes Stress-Induced Translational Repression","volume":"185","author":"Yamasaki","year":"2009","journal-title":"J. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2920","DOI":"10.1073\/pnas.91.8.2920","article-title":"Role of Glutamine-117 in the Ribonucleolytic Activity of Human Angiogenin","volume":"91","author":"Russo","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1073\/pnas.93.8.3243","article-title":"The C-Terminal Region of Human Angiogenin Has a Dual Role in Enzymatic Activity","volume":"93","author":"Russo","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.febslet.2008.12.043","article-title":"Stress Induces TRNA Cleavage by Angiogenin in Mammalian Cells","volume":"583","author":"Fu","year":"2009","journal-title":"FEBS Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.molcel.2011.06.022","article-title":"Angiogenin-Induced TRNA Fragments Inhibit Translation Initiation","volume":"43","author":"Ivanov","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"18201","DOI":"10.1073\/pnas.1407361111","article-title":"G-Quadruplex Structures Contribute to the Neuroprotective Effects of Angiogenin-Induced TRNA Fragments","volume":"111","author":"Ivanov","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"24655","DOI":"10.1016\/S0021-9258(18)35814-9","article-title":"Inactivation of Ribonuclease Inhibitor by Thiol-Disulfide Exchange","volume":"267","author":"Fominaya","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"42708","DOI":"10.1074\/jbc.M112.371799","article-title":"Genome-Wide Identification and Quantitative Analysis of Cleaved TRNA Fragments Induced by Cellular Stress","volume":"287","author":"Saikia","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/ncomms2126","article-title":"Structural and Molecular Insights into the Mechanism of Action of Human Angiogenin-ALS Variants in Neurons","volume":"3","author":"Thiyagarajan","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"srep41996","DOI":"10.1038\/srep41996","article-title":"Structural Insights into Human Angiogenin Variants Implicated in Parkinson\u2019s Disease and Amyotrophic Lateral Sclerosis","volume":"7","author":"Bradshaw","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1111\/j.1432-1033.1997.00712.x","article-title":"Three-Dimensional Solution Structure of Human Angiogenin Determined by 1H,15N-NMR Spectroscopy--Characterization of Histidine Protonation States and PKa Values","volume":"250","author":"Lequin","year":"1997","journal-title":"Eur. J. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s12104-016-9704-9","article-title":"NMR Study of Met-1 Human Angiogenin: (1)H, (13)C, (15)N Backbone and Side-Chain Resonance Assignment","volume":"10","author":"Tsika","year":"2016","journal-title":"Biomol. NMR Assign."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10048-007-0111-3","article-title":"Identification of New ANG Gene Mutations in a Large Cohort of Italian Patients with Amyotrophic Lateral Sclerosis","volume":"9","author":"Gellera","year":"2008","journal-title":"Neurogenetics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/ana.22611","article-title":"Angiogenin Variants in Parkinson Disease and Amyotrophic Lateral Sclerosis","volume":"70","author":"Schelhaas","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7401","DOI":"10.1021\/bi00444a038","article-title":"Site-Directed Mutagenesis of Histidine-13 and Histidine-114 of Human Angiogenin. Alanine Derivatives Inhibit Angiogenin-Induced Angiogenesis","volume":"28","author":"Shapiro","year":"1989","journal-title":"Biochemistry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1002\/pro.5560041202","article-title":"3D Domain Swapping: A Mechanism for Oligomer Assembly","volume":"4","author":"Bennett","year":"1995","journal-title":"Protein Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1042\/bj20031922","article-title":"Oligomerization of Bovine Ribonuclease A: Structural and Functional Features of Its Multimers","volume":"380","author":"Libonati","year":"2004","journal-title":"Biochem. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.bbapap.2005.10.011","article-title":"Three-Dimensional Domain-Swapped Oligomers of Ribonuclease A: Identification of a Fifth Tetramer, Pentamers and Hexamers, and Detection of Trace Heptameric, Octameric and Nonameric Species","volume":"1764","author":"Gotte","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1016\/j.febslet.2013.09.038","article-title":"Structural and Functional Relationships of Natural and Artificial Dimeric Bovine Ribonucleases: New Scaffolds for Potential Antitumor Drugs","volume":"587","author":"Gotte","year":"2013","journal-title":"FEBS Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/BF00175245","article-title":"The 13C Chemical-Shift Index: A Simple Method for the Identification of Protein Secondary Structure Using 13C Chemical-Shift Data","volume":"4","author":"Wishart","year":"1994","journal-title":"J. Biomol. NMR"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1110\/ps.13601","article-title":"Binding of Phosphate and Pyrophosphate Ions at the Active Site of Human Angiogenin as Revealed by X-Ray Crystallography","volume":"10","author":"Leonidas","year":"2001","journal-title":"Protein Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1073\/pnas.91.8.2915","article-title":"Crystal Structure of Human Angiogenin Reveals the Structural Basis for Its Functional Divergence from Ribonuclease","volume":"91","author":"Acharya","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/chir.22064","article-title":"Circular Dichroism Spectroscopy of DNA: From Duplexes to Quadruplexes","volume":"24","author":"Kypr","year":"2012","journal-title":"Chirality"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7171","DOI":"10.1002\/anie.201709184","article-title":"G-Quadruplex Secondary Structure Obtained from Circular Dichroism Spectroscopy","volume":"57","author":"Trent","year":"2018","journal-title":"Angew. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.biochi.2011.08.004","article-title":"The Stability of Intramolecular DNA G-Quadruplexes Compared with Other Macromolecules","volume":"94","author":"Lane","year":"2012","journal-title":"Biochimie"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1021\/cb500100z","article-title":"Discovery of Selective Ligands for Telomeric RNA G-Quadruplexes (TERRA) through 19F-NMR Based Fragment Screening","volume":"9","author":"Somoza","year":"2014","journal-title":"ACS Chem. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/j.1432-1033.1978.tb12111.x","article-title":"Synthetic RNA and DNA Duplexes. Premelting, Melting and Postmelting Transitions of Alternating Inosine-Cytosine Polynucleotides in Solution","volume":"83","author":"Patel","year":"1978","journal-title":"Eur. J. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1006\/jmbi.1996.0903","article-title":"On the Conformation of the Anticodon Loops of Initiator and Elongator Methionine TRNAs","volume":"267","author":"Schweisguth","year":"1997","journal-title":"J. Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1073\/pnas.92.7.2949","article-title":"Crystal Structure of Bovine Angiogenin at 1.5-A Resolution","volume":"92","author":"Acharya","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.jmb.2008.04.042","article-title":"The Solution Structure and Dynamics of Human Pancreatic Ribonuclease Determined by NMR Spectroscopy Provide Insight into Its Remarkable Biological Activities and Inhibition","volume":"379","author":"Bruix","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1021\/bi00280a021","article-title":"Structure of Ribonuclease A: Results of Joint Neutron and X-Ray Refinement at 2.0 a Resolution","volume":"22","author":"Wlodawer","year":"1983","journal-title":"Biochemistry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1006\/jmbi.1998.2365","article-title":"Hydrogen Exchange in Ribonuclease A and Ribonuclease S: Evidence for Residual Structure in the Unfolded State under Native Conditions","volume":"285","author":"Neira","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1002\/bip.21152","article-title":"The (1)H, (13)C, (15)N Resonance Assignment, Solution Structure, and Residue Level Stability of Eosinophil Cationic Protein\/RNase 3 Determined by NMR Spectroscopy","volume":"91","author":"Laurents","year":"2009","journal-title":"Biopolymers"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/B978-0-12-381262-9.00002-1","article-title":"Structural, Thermodynamic, and Mechanistical Studies in Uroporphyrinogen III Synthase: Molecular Basis of Congenital Erythropoietic Porphyria","volume":"83","author":"Fortian","year":"2011","journal-title":"Adv. Protein Chem. Struct. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/344363a0","article-title":"Reverse Hydrophobic Effects Relieved by Amino-Acid Substitutions at a Protein Surface","volume":"344","author":"Pakula","year":"1990","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.jmb.2011.04.027","article-title":"ALS-Causing SOD1 Mutations Promote Production of Copper-Deficient Misfolded Species","volume":"409","author":"Ip","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Casado, L., Serrano-Chac\u00f3n, I., Montalvillo-Jim\u00e9nez, L., Corzana, F., Bastida, A., Gonz\u00e1lez-Santana, A., Gonz\u00e1lez, C., Asensio, J.L., and Santana, A.G. (2020). De Novo Design of Selective Quadruplex-Duplex Junction Ligands and Structural Characterisation of Their Binding Mode: Targeting the G4 Hot-Spot. Chem. Weinh. Bergstr. Ger.","DOI":"10.1002\/chem.202005026"},{"key":"ref_57","first-page":"125","article-title":"An Amyloid-Like Pathological Conformation of TDP-43 Is Stabilized by Hypercooperative Hydrogen Bonds","volume":"9","author":"Baralle","year":"2016","journal-title":"Front. Mol. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.cell.2015.07.047","article-title":"A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation","volume":"162","author":"Patel","year":"2015","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.tibs.2012.03.003","article-title":"TDP-43: Gumming up Neurons through Protein-Protein and Protein-RNA Interactions","volume":"37","author":"Buratti","year":"2012","journal-title":"Trends Biochem. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.neuron.2020.08.022","article-title":"ALS Genetics: Gains, Losses, and Implications for Future Therapies","volume":"108","author":"Kim","year":"2020","journal-title":"Neuron"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5162","DOI":"10.1093\/emboj\/16.17.5162","article-title":"Molecular Recognition of Human Angiogenin by Placental Ribonuclease Inhibitor--an X-ray Crystallographic Study at 2.0 aResolution","volume":"16","author":"Papageorgiou","year":"1997","journal-title":"EMBO J."},{"key":"ref_62","first-page":"875","article-title":"The Crystal Structure of Human Angiogenin in Complex with an Antitumor Neutralizing Antibody","volume":"11","author":"Chavali","year":"2003","journal-title":"Struct. Lond. Engl. 1993"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0014-5793(99)01623-3","article-title":"Effective Expression and Purification of Recombinant Onconase, an Antitumor Protein","volume":"463","author":"Notomista","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_64","first-page":"1325","article-title":"NMRFAM-SPARKY: Enhanced Software for Biomolecular NMR Spectroscopy","volume":"31","author":"Lee","year":"2015","journal-title":"Bioinf. Oxf. Engl."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s10858-011-9472-x","article-title":"Random Coil Chemical Shift for Intrinsically Disordered Proteins: Effects of Temperature and PH","volume":"49","author":"Kjaergaard","year":"2011","journal-title":"J. Biomol. NMR"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/BF00242476","article-title":"The Use of 1JC Alpha H Alpha Coupling Constants as a Probe for Protein Backbone Conformation","volume":"3","author":"Vuister","year":"1993","journal-title":"J. Biomol. NMR"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5984","DOI":"10.1021\/bi00185a040","article-title":"Backbone Dynamics of a Free and Phosphopeptide-Complexed Src Homology 2 Domain Studied by 15N NMR Relaxation","volume":"33","author":"Farrow","year":"1994","journal-title":"Biochemistry"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/prot.340170110","article-title":"Primary Structure Effects on Peptide Group Hydrogen Exchange","volume":"17","author":"Bai","year":"1993","journal-title":"Proteins"},{"key":"ref_69","unstructured":"Zhang, Y.-Z. (1995). Protein and Peptide Structure and Interactions Studied by Hydrogen Exchanger and NMR. [Ph.D. Thesis, University of Pennsylvannia]."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jmr.2008.09.010","article-title":"Amino Acid Type Identification in NMR Spectra of Proteins via Beta- and Gamma-Carbon Edited Experiments","volume":"195","author":"Santoro","year":"2008","journal-title":"J. Magn. Reson."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1439\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:18:10Z","timestamp":1760159890000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/3\/1439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,1]]},"references-count":70,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["ijms22031439"],"URL":"https:\/\/doi.org\/10.3390\/ijms22031439","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202101.0078.v1","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,1]]}}}