David Craig, Mu Gao, Klaus Schulten, and Viola Vogel.
Tuning the mechanical stability of fibronectin type III modules
through sequence variation.
Structure, 12:21-30, 2004.
CRAI2004
Cells can switch the functional states of proteins by exerting
mechanical forces that stretch them out of their equilibrium state.
Using steered molecular dynamics, we investigated how variations
in the amino acid sequence of FnIII modules from the cell
adhesion protein fibronectin affect their mechanical stability.
Despite remarkably similar tertiary structures, FnIII modules share
low sequence homology. Conversely, the sequence homology for
the same FnIII module across multiple species is notably higher
suggesting that sequence variability is functionally significant.
Our studies find that the mechanical stability of FnIII modules can
be tuned by substitutions of just a few key amino acids by altering
access of hydrogen bond that break early in the unfolding
pathway to attack by water molecules. Furthermore, the FnIII
hierarchy of mechanical unfolding can be changed by
environmental conditions, such as pH for FnIII, or by
forming
complexes with other molecules, such as heparin binding to
FnIII.
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, or by
forming
complexes with other molecules, such as heparin binding to
FnIII
.
