{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:58:49Z","timestamp":1776214729274,"version":"3.50.1"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"JSPS","doi-asserted-by":"publisher","award":["KAKENHI 21K15028"],"award-info":[{"award-number":["KAKENHI 21K15028"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJCR1863"],"award-info":[{"award-number":["JPMJCR1863"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI JP20H03252, JP20KK0341, JP21H05047"],"award-info":[{"award-number":["KAKENHI JP20H03252, JP20KK0341, JP21H05047"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The Bin\u2013Amphiphysin\u2013Rvs (BAR) domain of endophilin binds to the cell membrane and shapes it into a tubular shape for endocytosis. Endophilin has a Src-homology 3 (SH3) domain at their C-terminal. The SH3 domain interacts with the proline-rich motif (PRM) that is found in proteins such as neural Wiskott\u2013Aldrich syndrome protein (N-WASP). Here, we re-examined the binding sites of the SH3 domain of endophilin in N-WASP by machine learning-based prediction and identified the previously unrecognized binding site. In addition to the well-recognized PRM at the central proline-rich region, we found a PRM in front of the N-terminal WASP homology 1 (WH1) domain of N-WASP (NtPRM) as a binding site of the endophilin SH3 domain. Furthermore, the diameter of the membrane tubules in the presence of NtPRM mutant was narrower and wider than that in the presence of N-WASP and in its absence, respectively. Importantly, the NtPRM of N-WASP was involved in the membrane localization of endophilin A2 in cells. Therefore, the NtPRM contributes to the binding of endophilin to N-WASP in membrane remodeling.<\/jats:p>","DOI":"10.1093\/jb\/mvad065","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T11:58:15Z","timestamp":1695902295000},"page":"57-67","source":"Crossref","is-referenced-by-count":4,"title":["The SH3 binding site in front of the WH1 domain contributes to the membrane binding of the BAR domain protein endophilin A2"],"prefix":"10.1093","volume":"175","author":[{"given":"Pei Fang","family":"Sim","sequence":"first","affiliation":[{"name":"Nara Institute of Science and Technology Graduate School of Science and Technology, , 8916-5 Takayama, Ikoma, Nara 630-0192,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Fey","family":"Chek","sequence":"additional","affiliation":[{"name":"Nara Institute of Science and Technology Institute for Research Initiatives, , 8916-5 Takayama, Ikoma, Nara 630-0192,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nhung Thi Hong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Nara Institute of Science and Technology Graduate School of Science and Technology, , 8916-5 Takayama, Ikoma, Nara 630-0192,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamako","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Nara Institute of Science and Technology Graduate School of Science and Technology, , 8916-5 Takayama, Ikoma, Nara 630-0192,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehiko","family":"Inaba","sequence":"additional","affiliation":[{"name":"Nara Institute of Science and Technology Graduate School of Science and Technology, , 8916-5 Takayama, Ikoma, Nara 630-0192,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshio","family":"Hakoshima","sequence":"additional","affiliation":[{"name":"Nara Institute of Science and Technology Institute for Research Initiatives, , 8916-5 Takayama, Ikoma, Nara 630-0192,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4612-0628","authenticated-orcid":false,"given":"Shiro","family":"Suetsugu","sequence":"additional","affiliation":[{"name":"Nara Institute of Science and Technology Graduate School of Science and Technology, , 8916-5 Takayama, Ikoma, Nara 630-0192,","place":["Japan"]},{"name":"Nara Institute of Science and Technology Data Science Center, , 8916-5 Takayama, Ikoma, Nara 630-0192,","place":["Japan"]},{"name":"Nara Institute of Science and Technology Center for Digital Green-innovation, , 8916-5 Takayama, Ikoma, Nara 630-0192,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,10,9]]},"reference":[{"key":"2026041420064945700_ref1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3390\/membranes2010091","article-title":"The BAR domain superfamily proteins from subcellular structures to human diseases","volume":"2","author":"Safari","year":"2012","journal-title":"Membranes"},{"key":"2026041420064945700_ref2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.tcb.2012.01.001","article-title":"Synergistic BAR-NPF interactions in actin-driven membrane remodeling","volume":"22","author":"Suetsugu","year":"2012","journal-title":"Trends Cell Biol."},{"key":"2026041420064945700_ref3","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/sj.embor.7400105","article-title":"The BAR-domain family of proteins: a case of bending and binding?","volume":"5","author":"Habermann","year":"2004","journal-title":"EMBO Rep."},{"key":"2026041420064945700_ref4","doi-asserted-by":"crossref","first-page":"2898","DOI":"10.1038\/sj.emboj.7601174","article-title":"Mechanism of endophilin N-BAR domain-mediated membrane curvature","volume":"25","author":"Gallop","year":"2006","journal-title":"EMBO J."},{"key":"2026041420064945700_ref5","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1038\/sj.emboj.7601176","article-title":"Endophilin BAR domain drives membrane curvature by two newly identified structure-based mechanisms","volume":"25","author":"Masuda","year":"2006","journal-title":"EMBO J."},{"key":"2026041420064945700_ref6","doi-asserted-by":"crossref","first-page":"6461","DOI":"10.1074\/jbc.M207433200","article-title":"Neural Wiskott-Aldrich syndrome protein is recruited to rafts and associates with endophilin A in response to epidermal growth factor","volume":"278","author":"Otsuki","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2026041420064945700_ref7","doi-asserted-by":"crossref","first-page":"4401","DOI":"10.1172\/JCI65289","article-title":"Role of dynamin, synaptojanin, and endophilin in podocyte foot processes","volume":"122","author":"Soda","year":"2012","journal-title":"J. Clin. Investig."},{"key":"2026041420064945700_ref8","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1242\/jcs.072686","article-title":"An endophilin\u2013dynamin complex promotes budding of clathrin-coated vesicles during synaptic vesicle recycling","volume":"124","author":"Sundborger","year":"2011","journal-title":"J. Cell Sci."},{"key":"2026041420064945700_ref9","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.devcel.2009.11.005","article-title":"Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits","volume":"17","author":"Ferguson","year":"2009","journal-title":"Dev. Cell"},{"key":"2026041420064945700_ref10","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1038\/emboj.2013.212","article-title":"Endophilin, Lamellipodin, and Mena cooperate to regulate F-actin-dependent EGF-receptor endocytosis","volume":"32","author":"Vehlow","year":"2013","journal-title":"EMBO J."},{"key":"2026041420064945700_ref11","doi-asserted-by":"crossref","first-page":"5326","DOI":"10.1002\/j.1460-2075.1996.tb00917.x","article-title":"N-WASP, a novel actin-depolymerizing protein, regulates the cortical cytoskeletal rearrangement in a PIP2-dependent manner downstream of tyrosine kinases","volume":"15","author":"Miki","year":"1996","journal-title":"EMBO J."},{"key":"2026041420064945700_ref12","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/ncb2290","article-title":"N-WASP regulates the epithelial junctional actin cytoskeleton through a non-canonical post-nucleation pathway","volume":"13","author":"Kovacs","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"2026041420064945700_ref13","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0092-8674(03)00120-X","article-title":"Cellular motility driven by assembly and disassembly of actin filaments","volume":"112","author":"Pollard","year":"2003","journal-title":"Cell"},{"key":"2026041420064945700_ref14","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1146\/annurev.biochem.77.060407.135452","article-title":"Physical mechanisms of signal integration by WASP family proteins","volume":"79","author":"Padrick","year":"2010","journal-title":"Annu. Rev. Biochem."},{"key":"2026041420064945700_ref15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nrm2069","article-title":"The WASP\u2013WAVE protein network: connecting the membrane to the cytoskeleton","volume":"8","author":"Takenawa","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026041420064945700_ref16","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1152\/physrev.00040.2013","article-title":"Dynamic shaping of cellular membranes by phospholipids and membrane-deforming proteins","volume":"94","author":"Suetsugu","year":"2014","journal-title":"Physiol. Rev."},{"key":"2026041420064945700_ref17","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/j.molcel.2018.05.013","article-title":"Direct phosphorylation of SRC homology 3 domains by tyrosine kinase receptors disassembles ligand-induced signaling networks","volume":"70","author":"Dionne","year":"2018","journal-title":"Mol. Cell"},{"key":"2026041420064945700_ref18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.0020048","article-title":"Protein family expansions and biological complexity","volume":"2","author":"Vogel","year":"2006","journal-title":"PLoS Comput. Biol."},{"key":"2026041420064945700_ref19","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/372375a0","article-title":"Structural determinants of peptide-binding orientation and of sequence specificity in SH3 domains","volume":"372","author":"Lim","year":"1994","journal-title":"Nature"},{"key":"2026041420064945700_ref20","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/0092-8674(93)90582-B","article-title":"Structure of the Pl3K SH3 domain and analysis of the SH3 family","volume":"72","author":"Koyama","year":"1993","journal-title":"Cell"},{"key":"2026041420064945700_ref21","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0014-5793(92)80901-R","article-title":"SH3\u2014an abundant protein domain in search of a function","volume":"307","author":"Musacchio","year":"1992","journal-title":"FEBS Lett."},{"key":"2026041420064945700_ref22","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0079-6107(94)90003-5","article-title":"Structure and function of the SH3 domain","volume":"61","author":"Musacchio","year":"1994","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"2026041420064945700_ref23","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1016\/j.str.2017.07.017","article-title":"Comprehensive analysis of the human SH3 domain family reveals a wide variety of non-canonical specificities","volume":"25","author":"Teyra","year":"2017","journal-title":"Structure"},{"key":"2026041420064945700_ref24","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005499","article-title":"Exhaustive search of linear information encoding protein-peptide recognition","volume":"13","author":"Kelil","year":"2017","journal-title":"PLoS Comput. Biol."},{"key":"2026041420064945700_ref25","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/s41467-021-21873-2","article-title":"Protein context shapes the specificity of SH3 domain-mediated interactions in vivo","volume":"12","author":"Dionne","year":"2021","journal-title":"Nat. Commun."},{"key":"2026041420064945700_ref26","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/msb.2013.9","article-title":"SH3 interactome conserves general function over specific form","volume":"9","author":"Xin","year":"2013","journal-title":"Mol. Syst. Biol."},{"key":"2026041420064945700_ref27","doi-asserted-by":"crossref","first-page":"re8","DOI":"10.1126\/stke.2003.179.re8","article-title":"The structure and function of proline recognition domains","volume":"2003","author":"Zarrinpar","year":"2003","journal-title":"Sci. STKE"},{"key":"2026041420064945700_ref28","article-title":"Improved prediction of protein-protein interactions using AlphaFold2","volume":"13","author":"Bryant","year":"2022","journal-title":"Nat. Commun."},{"key":"2026041420064945700_ref29","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"2026041420064945700_ref30","article-title":"Protein complex prediction with AlphaFold-multimer","author":"Evans","year":"2021","journal-title":"bioRxiv"},{"key":"2026041420064945700_ref31","doi-asserted-by":"crossref","DOI":"10.1016\/j.jmb.2021.167208","article-title":"AlphaFold and implications for intrinsically disordered proteins","volume":"433","author":"Ruff","year":"2021","journal-title":"J. Mol. Biol."},{"key":"2026041420064945700_ref32","doi-asserted-by":"crossref","DOI":"10.1016\/j.sbi.2022.102372","article-title":"AlphaFold models illuminate half of dark human proteins","volume":"74","author":"Binder","year":"2022","journal-title":"Curr. Opin. Struct. Biol."},{"key":"2026041420064945700_ref33","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/s41594-022-00849-w","article-title":"A structural biology community assessment of AlphaFold 2 applications","volume":"29","author":"Akdel","year":"2022","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2026041420064945700_ref34","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1002\/j.1460-2075.1993.tb05922.x","article-title":"Crystal structure of the SH3 domain in human FYN; comparison of the three-dimensional structures of SH3 domains in tyrosine kinases and SPECTRIN","volume":"12","author":"Noble","year":"1993","journal-title":"EMBO J."},{"key":"2026041420064945700_ref35","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-022-32541-4","article-title":"SH3 domain regulation of RhoGAP activity: crosstalk between p120RasGAP and DLC1 RhoGAP","volume":"13","author":"Chau","year":"2022","journal-title":"Nat. Commun."},{"key":"2026041420064945700_ref36","doi-asserted-by":"crossref","first-page":"14683","DOI":"10.1021\/bi980989q","article-title":"RT loop flexibility enhances the specificity of Src family SH3 domains for HIV-1 Nef","volume":"37","author":"Arold","year":"1998","journal-title":"Biochemistry"},{"key":"2026041420064945700_ref37","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.1016\/j.febslet.2012.04.042","article-title":"SH3 domain ligand binding: what's the consensus and where's the specificity?","volume":"586","author":"Saksela","year":"2012","journal-title":"FEBS Lett."},{"key":"2026041420064945700_ref38","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/S0960-9822(95)00073-X","article-title":"SH3 domains: minding your p's and q's","volume":"5","author":"Mayer","year":"1995","journal-title":"Curr. Biol."},{"key":"2026041420064945700_ref39","doi-asserted-by":"crossref","DOI":"10.1074\/jbc.RA120.016118","article-title":"Endophilin recruitment drives membrane curvature generation through coincidence detection of GPCR loop interactions and negative lipid charge","volume":"296","author":"Mondal","year":"2021","journal-title":"J. Biol. Chem."},{"key":"2026041420064945700_ref40","article-title":"Endophilin-A2-dependent tubular endocytosis promotes plasma membrane repair and parasite invasion","volume":"134","author":"Corrotte","year":"2020","journal-title":"J. Cell Sci."},{"key":"2026041420064945700_ref41","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/nature14067","article-title":"Endophilin marks and controls a clathrin-independent endocytic pathway","volume":"517","author":"Boucrot","year":"2015","journal-title":"Nature"},{"key":"2026041420064945700_ref42","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nature14064","article-title":"Endophilin-A2 functions in membrane scission in clathrin-independent endocytosis","volume":"517","author":"Renard","year":"2015","journal-title":"Nature"},{"key":"2026041420064945700_ref43","doi-asserted-by":"crossref","first-page":"9411","DOI":"10.1074\/jbc.M115.703108","article-title":"The binding of syndapin SH3 domain to dynamin proline-rich domain involves short and long distance elements","volume":"291","author":"Luo","year":"2016","journal-title":"J. Biol. Chem."},{"key":"2026041420064945700_ref44","doi-asserted-by":"crossref","first-page":"4938","DOI":"10.2741\/3053","article-title":"The SH3 domain\u2014a family of versatile peptide- and protein-recognition module","volume":"13","author":"Kaneko","year":"2008","journal-title":"Front. Biosci."},{"key":"2026041420064945700_ref45","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1242\/jcs.016709","article-title":"SNX9 regulates tubular invagination of the plasma membrane through interaction with actin cytoskeleton and dynamin 2","volume":"121","author":"Shin","year":"2008","journal-title":"J. Cell Sci."},{"key":"2026041420064945700_ref46","doi-asserted-by":"crossref","first-page":"25119","DOI":"10.1074\/jbc.M113.490474","article-title":"Dual role of BAR domain-containing proteins in regulating vesicle release catalyzed by the GTPase, Dynamin-2","volume":"288","author":"Neumann","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2026041420064945700_ref47","doi-asserted-by":"crossref","first-page":"8213","DOI":"10.1073\/pnas.1003478107","article-title":"Molecular basis for SH3 domain regulation of F-BAR\u2013mediated membrane deformation","volume":"107","author":"Rao","year":"2010","journal-title":"Proc. Natl. Acad. Sci."},{"key":"2026041420064945700_ref48","doi-asserted-by":"crossref","first-page":"6083","DOI":"10.1093\/emboj\/cdf604","article-title":"Syndapins integrate N-WASP in receptor-mediated endocytosis","volume":"21","author":"Kessels","year":"2002","journal-title":"EMBO J."},{"key":"2026041420064945700_ref49","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.cell.2007.03.040","article-title":"Curved EFC\/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis","volume":"129","author":"Shimada","year":"2007","journal-title":"Cell"},{"key":"2026041420064945700_ref50","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.tibs.2012.09.001","article-title":"Membrane curvature and its generation by BAR proteins","volume":"37","author":"Mim","year":"2012","journal-title":"Trends Biochem. Sci."},{"key":"2026041420064945700_ref51","doi-asserted-by":"crossref","first-page":"eadf5143","DOI":"10.1126\/sciadv.adf5143","article-title":"Small GTPase Cdc42, WASP, and scaffold proteins for higher-order assembly of the F-BAR domain protein","volume":"9","author":"Wan Mohamad Noor","year":"2023","journal-title":"Sci. Adv."},{"key":"2026041420064945700_ref52","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1016\/j.neuron.2022.06.010","article-title":"Dynamin is primed at endocytic sites for ultrafast endocytosis","volume":"110","author":"Imoto","year":"2022","journal-title":"Neuron"},{"key":"2026041420064945700_ref53","doi-asserted-by":"crossref","DOI":"10.1083\/jcb.202105035","article-title":"IRSp53 promotes postsynaptic density formation and actin filament bundling","volume":"221","author":"Feng","year":"2022","journal-title":"J. Cell Biol."},{"key":"2026041420064945700_ref54","doi-asserted-by":"crossref","first-page":"5017","DOI":"10.1038\/s41467-022-32529-0","article-title":"Multivalent interactions between molecular components involved in fast endophilin mediated endocytosis drive protein phase separation","volume":"13","author":"Mondal","year":"2022","journal-title":"Nat. Commun."}],"container-title":["The Journal of Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jb\/advance-article-pdf\/doi\/10.1093\/jb\/mvad065\/51960403\/mvad065.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jb\/article-pdf\/175\/1\/57\/55267097\/mvad065.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jb\/article-pdf\/175\/1\/57\/55267097\/mvad065.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:12:48Z","timestamp":1776211968000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jb\/article\/175\/1\/57\/7301479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,9]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,10,9]]},"published-print":{"date-parts":[[2024,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jb\/mvad065","relation":{},"ISSN":["0021-924X","1756-2651"],"issn-type":[{"value":"0021-924X","type":"print"},{"value":"1756-2651","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,1]]},"published":{"date-parts":[[2023,10,9]]}}}