دورية أكاديمية

Towards a structurally resolved human protein interaction network

التفاصيل البيبلوغرافية
العنوان: Towards a structurally resolved human protein interaction network
المؤلفون: Burke, David F, Bryant, Patrick, Barrio-Hernandez, Inigo, Memon, Danish, Pozzati, Gabriele, Shenoy, Aditi, Zhu, Wensi, Dunham, Alistair S, Albanese, Pascal, Keller, Andrew, Scheltema, Richard A, Bruce, James E, Leitner, Alexander, Kundrotas, Petras, Beltrao, Pedro, Elofsson, Arne
المساهمون: Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics
سنة النشر: 2023
مصطلحات موضوعية: Computational Biology/methods, Humans, Mutation, Protein Interaction Maps, Signal Transduction
الوصف: Cellular functions are governed by molecular machines that assemble through protein-protein interactions. Their atomic details are critical to studying their molecular mechanisms. However, fewer than 5% of hundreds of thousands of human protein interactions have been structurally characterized. Here we test the potential and limitations of recent progress in deep-learning methods using AlphaFold2 to predict structures for 65,484 human protein interactions. We show that experiments can orthogonally confirm higher-confidence models. We identify 3,137 high-confidence models, of which 1,371 have no homology to a known structure. We identify interface residues harboring disease mutations, suggesting potential mechanisms for pathogenic variants. Groups of interface phosphorylation sites show patterns of co-regulation across conditions, suggestive of coordinated tuning of multiple protein interactions as signaling responses. Finally, we provide examples of how the predicted binary complexes can be used to build larger assemblies helping to expand our understanding of human cell biology.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 1545-9993
العلاقة: https://dspace.library.uu.nl/handle/1874/434734Test
الإتاحة: https://dspace.library.uu.nl/handle/1874/434734Test
حقوق: info:eu-repo/semantics/OpenAccess
رقم الانضمام: edsbas.D88400BA
قاعدة البيانات: BASE