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Three-Dimensional Structures of Membrane Proteins from Genomic Sequencing
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Summary We show that amino acid co-variation in proteins, extracted from the evolutionary sequence record, can be used to fold transmembrane proteins. We use this technique to predict previously unknown, 3D structures for 11 transmembrane proteins (with up to 14 helices) from their sequences alone. The prediction method (EVfold_membrane), applies a maximum entropy approach to infer evolutionary co-variation in pairs of sequence positions within a protein family and then generates all-atom models with the derived pairwise distance constraints. We benchmark the approach with blinded, de novo computation of known transmembrane protein structures from 23 families, demonstrating unprecedented accuracy of the method for large transmembrane proteins. We show how the method can predict oligomerization, functional sites, and conformational changes in transmembrane proteins. With the rapid rise in large-scale sequencing, more accurate and more comprehensive information on evolutionary constraints can be decoded from genetic variation, greatly expanding the repertoire of transmembrane proteins amenable to modelling by this method.
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Metadata
- Authors
- Hopf, T. A., Colwell, L. J., Sheridan, R., Rost, B., Sander, C., & Marks, D. S.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 149
- Issue
- 7
- Pages
- 1607-1621
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2051545676
- Cited by
- 512
- References
- 12
- FWCI
- 19.52
- Type
- journal article
- Language
- en
- Open access
- bronze
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