{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:59:08Z","timestamp":1785473948821,"version":"3.56.0"},"reference-count":80,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"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":"crossref","award":["12401644"],"award-info":[{"award-number":["12401644"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31600670"],"award-info":[{"award-number":["31600670"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32271292"],"award-info":[{"award-number":["32271292"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["12401644"],"award-info":[{"award-number":["12401644"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["31600670"],"award-info":[{"award-number":["31600670"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["32271292"],"award-info":[{"award-number":["32271292"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"crossref","award":["BK20255001"],"award-info":[{"award-number":["BK20255001"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Protein self-interaction to form homodimers and higher-order homo-oligomers is a ubiquitous phenomenon fundamental to living organisms. Recent structural, system-level, and computational insights reveal that self-interacting proteins dictate the specificity, rewiring, and topological complexity of cellular signaling networks and macromolecular assemblies. Beyond their physiological roles, aberrant or dysregulated homotypic interactions disrupt cellular proteostasis, driving the formation of toxic non-native oligomers, pathological amyloid fibrillization, or aberrant liquid\u2013liquid phase separation transitions linked to neurodegenerative and systemic diseases. This review provides a comprehensive overview of the state-of-the-art experimental methodologies, including proximity labeling, as well as the advanced computational frameworks, such as deep learning architectures and protein language models, used to map the structural dynamics of SIPs. Furthermore, we dissect the evolutionary trajectories of SIPs within protein\u2013protein interaction networks, which are underpinned by dosage-balance constraints, and highlight their diverse functional advantages, ranging from allosteric modulation to biomolecular condensation. Finally, we summarize the molecular mechanisms linking pathological self-associations to human disorders, underscoring the emerging paradigm of targeting homotypic interfaces as a promising frontier for precision therapeutics.<\/jats:p>","DOI":"10.3390\/ijms27156776","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T08:16:52Z","timestamp":1785313012000},"page":"6776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Protein Self-Interaction in Cellular Function and Network Evolution: Molecular Mechanisms, AI-Driven Insights, and Therapeutic Potentials"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6719-8299","authenticated-orcid":false,"given":"Yuanxiao","family":"Gao","sequence":"first","affiliation":[{"name":"School of Mathematics and Data Science, Shaanxi University of Science and Technology, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2507-3033","authenticated-orcid":false,"given":"Wenyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Northwestern Polytechnical University, Xi\u2019an 710129, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8754-1541","authenticated-orcid":false,"given":"Guang","family":"Hu","sequence":"additional","affiliation":[{"name":"Biomedical Basic Research Center (BBRC) of Jiangsu, MOE Key Laboratory of Geriatric Diseases and Immunology, School of Life Sciences, Soochow University, Suzhou 215123, China"},{"name":"Institute of Health Data Science at Soochow University, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/372409a0","article-title":"Protein-protein interaction. Complex flexibility","volume":"372","author":"Jurnak","year":"1994","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrg1272","article-title":"Network biology: Understanding the cell\u2019s functional organization","volume":"5","author":"Barabasi","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"035007","DOI":"10.1088\/1478-3975\/8\/3\/035007","article-title":"Caught in self-interaction: Evolutionary and functional mechanisms of protein homooligomerization","volume":"8","author":"Hashimoto","year":"2011","journal-title":"Phys. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1016\/j.bpj.2020.01.046","article-title":"Modulation of toroidal proteins dynamics in favor of functional mechanisms upon ligand binding","volume":"118","author":"Li","year":"2020","journal-title":"Biophys. J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.cell.2024.01.022","article-title":"An atlas of protein homo-oligomerization across domains of life","volume":"187","author":"Schweke","year":"2024","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1074\/mcp.M112.021790","article-title":"Proteome-wide prediction of self-interacting proteins based on multiple properties","volume":"12","author":"Liu","year":"2013","journal-title":"Mol. Cell. Proteom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1111\/febs.12744","article-title":"Weak protein complexes: Challenging to study but essential for life","volume":"281","author":"Qin","year":"2014","journal-title":"FEBS J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.trechm.2024.05.002","article-title":"Mass spectrometry-based methods for characterizing transient protein\u2013protein interactions","volume":"6","author":"Veale","year":"2024","journal-title":"Trends Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.tibs.2004.09.006","article-title":"The power of two: Protein dimerization in biology","volume":"29","author":"Marianayagam","year":"2004","journal-title":"Trends Biochem. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3629","DOI":"10.1093\/nar\/gki678","article-title":"Binding properties and evolution of homodimers in protein-protein interaction networks","volume":"33","author":"Ispolatov","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Perez-Bercoff, A., Makino, T., and McLysaght, A. (2010). Duplicability of self-interacting human genes. BMC Evol. Biol., 10.","DOI":"10.1186\/1471-2148-10-160"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gotte, G., and Menegazzi, M. (2023). Protein oligomerization. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310648"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/340245a0","article-title":"A novel genetic system to detect protein-protein interactions","volume":"340","author":"Fields","year":"1989","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1095\/biolreprod58.2.302","article-title":"Yeast two-hybrid: So many interactions, (in) so little time","volume":"58","author":"Young","year":"1998","journal-title":"Biol. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/nmeth.2895","article-title":"The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells","volume":"11","author":"Petschnigg","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10340","DOI":"10.1073\/pnas.91.22.10340","article-title":"Split ubiquitin as a sensor of protein interactions in vivo","volume":"91","author":"Johnsson","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1002\/pmic.201100523","article-title":"Affinity purification coupled to mass spectrometry: Basic principles and strategies","volume":"12","author":"Dunham","year":"2012","journal-title":"Proteomics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1074\/mcp.M114.041012","article-title":"EASY-affinity purification of protein complexes at endogenous expression levels for quantitative mass spectrometry","volume":"14","author":"Keilhauer","year":"2015","journal-title":"Mol. Cell. Proteom."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1083\/jcb.201112098","article-title":"A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells","volume":"196","author":"Roux","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nbt.4201","article-title":"Efficient proximity labeling in living cells and organisms with TurboID","volume":"36","author":"Branon","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41592-020-01010-5","article-title":"Deciphering molecular interactions by proximity labeling","volume":"18","author":"Qin","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4285","DOI":"10.1073\/pnas.96.8.4285","article-title":"Assigning protein functions by comparative genome analysis: Protein phylogenetic profiles","volume":"96","author":"Pellegrini","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"W160","DOI":"10.1093\/nar\/gkv455","article-title":"ProtPhylo: Identification of protein-phenotype and protein-protein functional associations via phylogenetic profiling","volume":"43","author":"Cheng","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/47056","article-title":"Protein interaction maps for complete genomes based on gene fusion events","volume":"402","author":"Enright","year":"1999","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1126\/science.285.5428.751","article-title":"Detecting protein function and protein-protein interactions from genome sequences","volume":"285","author":"Marcotte","year":"1999","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chen, Z., You, Z., Zhang, Q., Guo, Z., Wang, S., and Wang, Y. (2023). In silico prediction methods of self-interacting proteins: An empirical survey. Front. Comput. Sci., 17.","DOI":"10.1007\/s11704-022-1563-1"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1007\/s00726-016-2226-z","article-title":"SPAR: A random forest-based predictor for self-interacting proteins with fine-grained domain information","volume":"48","author":"Liu","year":"2016","journal-title":"Amino Acids"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"D374","DOI":"10.1093\/nar\/gkt887","article-title":"3did: A catalog of domain-based interactions of known three-dimensional structure","volume":"42","author":"Mosca","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_29","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":"ref_30","doi-asserted-by":"crossref","first-page":"1176934320984171","DOI":"10.1177\/1176934320984171","article-title":"NLPEI: A novel self-interacting protein prediction model based on natural language processing and evolutionary information","volume":"16","author":"Jia","year":"2020","journal-title":"Evol. Bioinform."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1176934320924674","DOI":"10.1177\/1176934320924674","article-title":"Predicting self-interacting proteins using a recurrent neural network and protein evolutionary information","volume":"16","author":"An","year":"2020","journal-title":"Evol. Bioinform."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.pbiomolbio.2025.07.003","article-title":"Computational protein design: Advancing biotechnology through in silico engineering","volume":"197","author":"Ranbhor","year":"2025","journal-title":"Prog. Biolphys. Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1038\/s41467-025-57148-3","article-title":"Rapid and accurate prediction of protein homo-oligomer symmetry using Seq2Symm","volume":"16","author":"Kshirsagar","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/B978-0-12-386931-9.00002-7","article-title":"Structural, evolutionary, and assembly principles of protein oligomerization","volume":"117","author":"Levy","year":"2013","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gibson, T.A., and Goldberg, D.S. (2009). Questioning the ubiquity of neofunctionalization. PLoS Comput. Biol., 5.","DOI":"10.1371\/journal.pcbi.1000252"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Rice, A.M., and McLysaght, A. (2017). Dosage-sensitive genes in evolution and disease. BMC Biol., 15.","DOI":"10.1186\/s12915-017-0418-y"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nmeth.4510","article-title":"PDB-wide identification of biological assemblies from conserved quaternary structure geometry","volume":"15","author":"Dey","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"101966","DOI":"10.1016\/j.gde.2022.101966","article-title":"How gene duplication diversifies the landscape of protein oligomeric state and function","volume":"76","author":"Mallik","year":"2022","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"msad070","DOI":"10.1093\/molbev\/msad070","article-title":"An assessment of quaternary structure functionality in homomer protein complexes","volume":"40","author":"Abrusan","year":"2023","journal-title":"Mol. Biol. Evol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1146\/annurev-genet-111212-133301","article-title":"New gene evolution: Little did we know","volume":"47","author":"Long","year":"2013","journal-title":"Annu. Rev. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1126\/science.3289117","article-title":"The leucine zipper: A hypothetical structure common to a new class of DNA binding proteins","volume":"240","author":"Landschulz","year":"1988","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41586-020-3021-2","article-title":"A hydrophobic ratchet entrenches molecular complexes","volume":"588","author":"Hochberg","year":"2020","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"20352","DOI":"10.1073\/pnas.1012999107","article-title":"Mechanisms of protein oligomerization, the critical role of insertions and deletions in maintaining different oligomeric states","volume":"107","author":"Hashimoto","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3022","DOI":"10.1016\/j.cell.2021.04.011","article-title":"Dual proteome-scale networks reveal cell-specific remodeling of the human interactome","volume":"184","author":"Huttlin","year":"2021","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1146\/annurev.biophys.29.1.105","article-title":"Structural symmetry and protein function","volume":"29","author":"Goodsell","year":"2000","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/35075138","article-title":"Lethality and centrality in protein networks","volume":"411","author":"Jeong","year":"2001","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s13059-015-0772-4","article-title":"New genes drive the evolution of gene interaction networks in the human and mouse genomes","volume":"16","author":"Zhang","year":"2015","journal-title":"Genome Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1093\/molbev\/msn122","article-title":"Natural selection against protein aggregation on self-interacting and essential proteins in yeast, fly, and worm","volume":"25","author":"Chen","year":"2008","journal-title":"Mol. Biol. Evol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"14250","DOI":"10.1073\/pnas.231465798","article-title":"Dimer formation drives the activation of the cell death protease caspase 9","volume":"98","author":"Renatus","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3303","DOI":"10.1016\/j.cell.2024.04.026","article-title":"FilamentID reveals the composition and function of metabolic enzyme polymers during gametogenesis","volume":"187","author":"Hugener","year":"2024","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e106044","DOI":"10.7554\/eLife.106044.4","article-title":"Dimerization and dynamics of human angiotensin-I converting enzyme revealed by cryo-EM and MD simulations","volume":"14","author":"Mancl","year":"2025","journal-title":"eLife"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41586-020-2188-x","article-title":"A reference map of the human binary protein interactome","volume":"580","author":"Luck","year":"2020","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0163-7258(01)00160-7","article-title":"G-protein-coupled receptor dimerization: Modulation of receptor function","volume":"92","author":"Rios","year":"2001","journal-title":"Pharmacol. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1124\/mol.104.000497","article-title":"G protein-coupled receptor dimerization: Function and ligand pharmacology","volume":"66","author":"Milligan","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"ref_56","first-page":"141","article-title":"G protein-coupled receptor dimerization and signaling","volume":"332","author":"Mellado","year":"2006","journal-title":"Methods Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1007\/s00018-004-4189-6","article-title":"Signal transduction via the stem cell factor receptor\/c-Kit","volume":"61","author":"Ronnstrand","year":"2004","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.cytogfr.2003.10.001","article-title":"The Class II cytokine receptor (CRF2) family: Overview and patterns of receptor-ligand interactions","volume":"15","author":"Langer","year":"2004","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"8299","DOI":"10.1038\/s41467-024-52584-z","article-title":"Cryo-EM structure of human class C orphan GPCR GPR179 involved in visual processing","volume":"15","author":"Yun","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_60","first-page":"412","article-title":"Structural insights into the regulation of monomeric and dimeric apelin receptor","volume":"16","author":"Wang","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.cell.2018.12.035","article-title":"Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates","volume":"176","author":"Alberti","year":"2019","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev-biophys-121219-081629","article-title":"Physical principles underlying the compartmentalization of intracellular phase separation","volume":"49","author":"Choi","year":"2020","journal-title":"Annu. Rev. Biophys."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"eaaf4382","DOI":"10.1126\/science.aaf4382","article-title":"Liquid\u2013liquid phase separation in molecular cell biology","volume":"357","author":"Shin","year":"2017","journal-title":"Science"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1006\/jmbi.2001.5134","article-title":"Regulated assembly of transcription factors and control of transcription initiation","volume":"314","author":"Beckett","year":"2001","journal-title":"J. Mol. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10489","DOI":"10.1073\/pnas.90.22.10489","article-title":"Topography of the histone octamer surface: Repeating structural motifs utilized in the docking of nucleosomal DNA","volume":"90","author":"Arents","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nature01595","article-title":"The structure of DNA in the nucleosome core","volume":"423","author":"Richmond","year":"2003","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"337","DOI":"10.2307\/1543106","article-title":"Actin: Dissecting the structural basis of its oligomerization, polymerization, and polymorphism","volume":"194","author":"Steinmetz","year":"1998","journal-title":"Biol. Bull."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8531","DOI":"10.1073\/pnas.0503319102","article-title":"Specificity of cell-cell adhesion by classical cadherins: Critical role for low-affinity dimerization through beta-strand swapping","volume":"102","author":"Chen","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"11594","DOI":"10.1073\/pnas.0905349106","article-title":"Linking molecular affinity and cellular specificity in cadherin-mediated adhesion","volume":"106","author":"Katsamba","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s00401-017-1709-7","article-title":"Interactions of pathological proteins in neurodegenerative diseases","volume":"134","author":"Attems","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_71","first-page":"e26561","article-title":"Protein aggregation and neurodegenerative disease: Structural outlook for the novel therapeutics","volume":"92","author":"Arar","year":"2023","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Jiang, L.-L., Zhang, X.-L., and Hu, H.-Y. (2024). Co-aggregation of TDP-43 with other pathogenic proteins and their co-pathologies in neurodegenerative diseases. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252212380"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"211","DOI":"10.4161\/pri.18987","article-title":"Domain swapping and amyloid fibril conformation","volume":"6","year":"2012","journal-title":"Prion"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1126\/science.1072994","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease: Progress and problems on the road to therapeutics","volume":"297","author":"Hardy","year":"2002","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nn.3028","article-title":"The toxic Abeta oligomer and Alzheimer\u2019s disease: An emperor in need of clothes","volume":"15","author":"Benilova","year":"2012","journal-title":"Nat. Neurosci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4342","DOI":"10.1073\/pnas.0407287102","article-title":"Disease-associated mutations cause premature oligomerization of myelin proteolipid protein in the endoplasmic reticulum","volume":"102","author":"Swanton","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/s00109-012-0976-y","article-title":"Parkinson\u2019s disease-associated mutations in DJ-1 modulate its dimerization in living cells","volume":"91","author":"Repici","year":"2013","journal-title":"J. Mol. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41583-021-00432-0","article-title":"The molecular biology of FMRP: New insights into fragile X syndrome","volume":"22","author":"Richter","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/ajh.25687","article-title":"Hemoglobin S polymerization and sickle cell disease: A retrospective on the occasion of the 70th anniversary of Pauling\u2019s Science paper","volume":"95","author":"Eaton","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.immuni.2011.02.017","article-title":"Structure of a domain-swapped FOXP3 dimer on DNA and its function in regulatory T cells","volume":"34","author":"Bandukwala","year":"2011","journal-title":"Immunity"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6776\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:24:04Z","timestamp":1785471844000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":80,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156776"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156776","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]}}}