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Publication Abstract from PubMed

Dendroaspin (Den) and rhodostomin (Rho) are snake venom proteins containing a PRGDMP motif. Although Den and Rho have different 3D structures, they are highly potent integrin inhibitors. To study their structure, function, and dynamics relationships, we expressed Den and Rho in Pichia pastoris. The recombinant Den and Rho inhibited platelet aggregation with the K(I) values of 149.8 and 83.2 nM. Cell adhesion analysis showed that Den was 3.7 times less active than Rho when inhibiting the integrin alphaIIbbeta3 and 2.5 times less active when inhibiting the integrin alphavbeta3. In contrast, Den and Rho were similarly active when inhibiting the integrin alpha5beta1 with the IC(50) values of 239.8 and 256.8 nM. NMR analysis showed that recombinant Den and Rho have different 3D conformations for their arginyl-glycyl-aspartic acid (RGD) motif. However, the comparison with Rho showed that the docking of Den into integrin alphavbeta3 resulted in a similar number of contacts. Analysis of the dynamic properties of the RGD loop in Den and Rho showed that they also had different dynamic properties. These results demonstrate that protein scaffolds affect the function, structure, and dynamics of their RGD motif.

Dynamics and functional differences between dendroaspin and rhodostomin: Insights into protein scaffolds in integrin recognition.,Cheng CH, Chen YC, Shiu JH, Chang YT, Chang YS, Huang CH, Chen CY, Chuang WJ Protein Sci. 2012 Dec;21(12):1872-84. doi: 10.1002/pro.2169. Epub 2012 Nov 6. PMID:23033223^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.