Effect of p to a mutation of the n-terminal residue adjacent to the rgd motif on rhodostomin: Importance of dynamics in integrin recognition

Jia Hau Shiu, Chiu Yueh Chen, Yi Chun Chen, Yao Tsung Chang, Yung Sheng Chang, Chun Hao Huang, Woei Jer Chuang

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9 Citations (Scopus)

Abstract

Rhodostomin (Rho) is an RGD protein that specifically inhibits integrins. We found that Rho mutants with the P48A mutation 4.4-11.5 times more actively inhibited integrin α5β1. Structural analysis showed that they have a similar 3D conformation for the RGD loop. Docking analysis also showed no difference between their interactions with integrin α5β1. However, the backbone dynamics of RGD residues were different. The values of the R 2 relaxation parameter for Rho residues R49 and D51 were 39% and 54% higher than those of the P48A mutant, which caused differences in S 2, R ex, and τ e. The S 2 values of the P48A mutant residues R49, G50, and D51 were 29%, 14%, and 28% lower than those of Rho. The R ex values of Rho residues R49 and D51 were 0.91 s -1 and 1.42 s -1; however, no R ex was found for those of the P48A mutant. The τ e values of Rho residues R49 and D51 were 9.5 and 5.1 times lower than those of P48A mutant. Mutational study showed that integrin α5β1 prefers its ligands to contain (G/A)RGD but not PRGD sequences for binding. These results demonstrate that the N-terminal proline residue adjacent to the RGD motif affect its function and dynamics, which suggests that the dynamic properties of the RGD motif may be important in Rho's interaction with integrin α5β1.

Original languageEnglish
Article numbere28833
JournalPloS one
Volume7
Issue number1
DOIs
Publication statusPublished - 2012 Jan 4

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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