Molecular and structural insight into the role of key residues of thrombospondin-1 and calreticulin in thrombospondin-1-calreticulin binding.

ABSTRACT: Thrombospondin-1 (TSP1) binding to calreticulin (CRT) on the cell surface signals focal adhesion disassembly, leading to the intermediate adhesive phenotype, cell migration, anoikis resistance, and collagen stimulation. Residues Lys 24 and 32 in TSP1 and amino acids 24-26 and 32-34 in CRT have been shown through biochemical and cell-based approaches to be critical for TSP1-CRT binding and signaling. This study investigated the molecular and structural basis for these key TSP1 and CRT residues in TSP1-CRT binding. On the basis of a validated TSP1-CRT complex structure, we adopted steered molecular dynamics simulations to determine the effect of mutation of these key residues on TSP1-CRT binding and validated the simulation results with experimental observations. We further performed 30 ns m

SUBMITTER: Yan Q 

PROVIDER: S-EPMC3037594 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature