The Evolution of Protein Flexibility
EMSL Project ID
2138
Abstract
When novel genes are sequenced their structure and function can often be reliably predicted based on sequence similarity and evolutionary relationships to proteins with known structures. Currently, this process assumes that the proteins being compared adopt compact rigid structures and tends to ignore proteins that have partially collapsed, flexible structures. This is despite the fact that known flexible proteins and protein domains have important biological functions and that analysis of genome sequence data has revealed proteins with flexible regions longer than fifty amino acids are common in nature. The lack of information characterizing the partially collapsed flexible structures of proteins inhibits our ability to predict their existence based on sequence data. It also limits our understanding of how the sequences of such regions specify function, the presence of residual structure, and the degree of flexibility. To begin addressing these questions we propose to investigate the structure, dynamics, and function of a conserved flexible linker from the 70kDa subunit of replication protein A (RPA70). For the handful of sequenced RPA70 homologues the similarity of the linker varies significantly, going from 43% sequence identity between the H. sapien and X. laevis linkers to no significant similarity between the H. sapien and S. cerevisiae linkers. It is unclear what selective processes have resulted in the observed sequence variation for the RPA70 linkers. It is also unclear how the observed sequence variation affects the structure and function of the linkers. If natural selection works to preserve flexible structures then one would expect that the linkers from different species have acquired the same level of flexibility using different sequences. By testing this hypothesis we will begin understanding the rules governing the evolution of protein flexibility.
Project Details
Project type
Capability Research
Start Date
2001-07-11
End Date
2002-11-18
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members