2ck2

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spinqualitylabelsall models 2ck2, resolution 2.0Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

STRUCTURE OF CORE-SWAPPED MUTANT OF FIBRONECTIN

Overview

The extracellular matrix proteins tenascin and fibronectin experience, significant mechanical forces in vivo. Both contain a number of tandem, repeating homologous fibronectin type III (fnIII) domains, and atomic, force microscopy experiments have demonstrated that the mechanical, strength of these domains can vary significantly. Previous work has shown, that mutations in the core of an fnIII domain from human tenascin (TNfn3), reduce the unfolding force of that domain significantly: The composition, of the core is apparently crucial to the mechanical stability of these, proteins. Based on these results, we have used rational redesign to, increase the mechanical stability of the 10th fnIII domain of human, fibronectin, FNfn10, which is directly involved in integrin binding. The, hydrophobic core of FNfn10 was replaced with that of the homologous, mechanically stronger TNfn3 domain. Despite the extensive substitution, FNoTNc retains both the three-dimensional structure and the cell adhesion, activity of FNfn10. Atomic force microscopy experiments reveal that the, unfolding forces of the engineered protein FNoTNc increase by, approximately 20% to match those of TNfn3. Thus, we have specifically, designed a protein with increased mechanical stability. Our results, demonstrate that core engineering can be used to change the mechanical, strength of proteins while retaining functional surface interactions.

About this Structure

2CK2 is a Single protein structure of sequence from Homo sapiens with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Designing an extracellular matrix protein with enhanced mechanical stability., Ng SP, Billings KS, Ohashi T, Allen MD, Best RB, Randles LG, Erickson HP, Clarke J, Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9633-7. Epub 2007 May 29. PMID:17535921

Page seeded by OCA on Wed Jan 23 14:52:35 2008