Tuning the mechanical stability of fibronectin type III modules through sequence variations

TitleTuning the mechanical stability of fibronectin type III modules through sequence variations
Publication TypeJournal Article
Year of Publication2004
AuthorsCraig, D, Gao M, Schulten K, Vogel V
JournalStructure (London, England : 1993)
Volume12
Pagination21-30
Date Published2004 Jan
Abstract

Cells can switch the functional states of extracellular matrix proteins by stretching them while exerting mechanical force. Using steered molecular dynamics, we investigated how the mechanical stability of FnIII modules from the cell adhesion protein fibronectin is affected by natural variations in their amino acid sequences. 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 through substitutions of just a few key amino acids by altering access of water molecules to hydrogen bonds that break early in the unfolding pathway. Furthermore, the FnIII hierarchy of mechanical unfolding can be changed by environmental conditions, such as pH for FnIII10, or by forming complexes with other molecules, such as heparin binding to FnIII13.

Pub Med Link

http://www.ncbi.nlm.nih.gov/pubmed/14725762?dopt=Abstract

Alternate JournalStructure
Citekey14725762