期刊
PROTEOMICS
卷 10, 期 1, 页码 72-80出版社
WILEY
DOI: 10.1002/pmic.200900146
关键词
Arg-Gly-Asp; In silico docking simulation; Integrin alpha v beta 3; Protein arrays; ProteoChip; Ser-Asp-Val
资金
- Korea Biotech RD Group [F104AB010004-29407A0201-00410]
A functional proteomic technology using protein chip and molecular simulation was used to demonstrate a novel biomolecular interaction between P11, a peptide containing the Ser-Asp-Val (SDV) sequence and integrin alpha v beta 3. P11 (HSDVHK) is a novel antagonistic peptide of integrin alpha v beta 3 screened from hexapeptide library through protein chip system. An in silico docking study and competitive protein chip assay revealed that the SDV sequence of P11 is able to create a stable inhibitory complex onto the vitronectin-binding site of integrin alpha v beta 3. The Arg-Gly-Asp (RGD)-binding site recognition by P 11 was site specific because the P 11 was inactive for the complex formation of a denatured form of integrin-vitronectin. P 11 showed a strong antagonism against alpha v beta 3-GRGDSP in teraction with an IC50 value of 25.72 +/- 3.34 nM, whereas the value of GRGDSP peptide was 1968.73 +/- 444.32 nM. The binding-free energies calculated from the docking simulations for each P11 and RGD peptide were -3.99 and -3.10 kcal/mol, respectively. The free energy difference between P11 and RGD corresponds to approximately a 4.5-fold lower K-i value for the P11 than the RGD peptide. The binding orientation of the docked P11 was similar to the crystal structure of the RGD in alpha v beta 3. The analyzed docked poses suggest that a divalent metal-ion coordination was a common driving force for the formation of both SDV/alpha v beta 3 and RGD/alpha v beta 3 complexes. This is the first report on the specific recognition of the RGD-binding site of alpha v beta 3 by a non-RGD containing peptide using a computer-assisted proteomic approach.
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