Inferring amino acid interactions underlying protein function
| Autor: | Rama Ranganathan, Victor H Salinas |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Genetics
chemistry.chemical_classification 0303 health sciences Basis (linear algebra) Sequence analysis Computational biology Protein superfamily Biology Amino acid 03 medical and health sciences 0302 clinical medicine chemistry Statistical coupling analysis Pairwise comparison 030217 neurology & neurosurgery Function (biology) Coevolution 030304 developmental biology |
| DOI: | 10.1101/215368 |
| Popis: | Protein function arises from a poorly defined pattern of cooperative energetic interactions between amino acid residues. Strategies for deducing this pattern have been proposed, but lack of benchmark data has limited experimental verification. Here, we extend deep-mutation technologies to enable measurement of many thousands of pairwise amino acid couplings in members of a protein family. The data show that despite great evolutionary divergence, homologous proteins conserve a sparse, spatially distributed network of cooperative interactions between amino acids that underlies function. This pattern is quantitatively captured in the coevolution of amino acid positions, especially as indicated by the statistical coupling analysis (SCA), providing experimental confirmation of the key tenets of this method. This work establishes a clear link between physical constraints on protein function and sequence analysis, enabling a general practical approach for understanding the structural basis for protein function. |
| Databáze: | OpenAIRE |
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