Coevolution in protein sequences
The function of proteins arises from the interaction between their amino acids. What form do these interactions take? How to infer them?
Protein sectors
What interaction patterns underlie protein function? An analysis of coevolution in multiple sequence alignments indicates that functional constraints reside primarily in collectively coupled subsets of amino acids, which we call sectors. A protein may contain a single sector or multiple sectors associated with different properties, and a sector may span two different protein domains.
References:
- N. Halabi, O. Rivoire, S. Leibler, R. Ranganathan (2009). Protein sectors: evolutionary units of three-dimensional structures.
- R. Smock, O. Rivoire, W. Russ, J. Swain, S. Leibler, R. Ranganathan, L. Gierasch (2010). An interdomain sector mediating allostery in HSP70 molecular chaperone.
- O. Rivoire, K. Reynolds, R. Ranganathan (2016). Evolution-based functional decomposition of proteins..
Scales of coevolution
How is inference of collective units – sectors – compatible with inference of isolated short-range contacts from the same multi-sequence protein alignment? Both patterns are generally present and their distributions are in agreement, but limited sampling of sequence space is always an issue and methods to correct for it typically emphasize one type of pattern at the expense of the other.
References:
- O. Rivoire (2013). Elements of coevolution in biological sequences.
- Y. Kleeorin, W. P. Russ, O. Rivoire, R. Ranganathan (2022). Undersampling and the inference of coevolution in proteins.