CRePE Project 3:
The Evolution of Protein Flexibility
The main goal of
this project is to investigate the
evolutionary constraints and patterns
that govern the natural selection of
partially collapsed, flexible proteins
and protein domains. To accomplish
this goal we have selected a model
system based on a conserved flexible
linker from the 70kDa subunit of
replication protein A (RPA70). We will
use this model system to determine if
and how natural selection works to
preserve the structure and function of
partially collapsed, flexible proteins
and protein domains through the
following specific aims:
-
Characterize the structure, dynamics,
and function of the linkers from several
RPA70 homologues and determine the
functional consequences of linker
swapping;
-
Investigate the allowable sequence space
of the RPA70 flexible linkers by
experimental evolution and by conducting
a broad survey of eukaryotic linker
sequences;
-
Use the results of specific aims 1 and 2
to formulate rules that permit the
identification and alignment of flexible
sequences as well as the de novo design
of sequences that function as linkers.
While the presence
and importance of partially collapsed,
flexible proteins and protein domains in
nature is well established, this
proposal marks the first systematic
empirical investigation into their
evolutionary constraints and patterns.
Contact:
Dr. Gary Daughdrill (MMBB)
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