2LA1

Expression in Pichia pastoris and backbone dynamics of dendroaspin, a three finger toxin

2LA1 の概要

• エントリーDOI: 10.2210/pdb2la1/pdb
• NMR情報: BMRB: 6915
• 分子名称: Mambin (1 entity in total)
• 機能のキーワード: dendroaspin, disintegrin, integrin, three-finger fold, snake toxin, toxin
• 由来する生物種: Dendroaspis jamesoni kaimosae (Eastern Jameson's mamba)
• 細胞内の位置: Secreted: P28375
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 6761.68

構造登録者

Chuang, W.J.,Cheng, C.H.,Chen, Y.C.,Shiu, J.H. (登録日: 2011-03-01, 公開日: 2012-03-07, 最終更新日: 2024-11-06)

主引用文献

Cheng, C.H.,Chen, Y.C.,Shiu, J.H.,Chang, Y.T.,Chang, Y.S.,Huang, C.H.,Chen, C.Y.,Chuang, W.J.
Dynamics and functional differences between dendroaspin and rhodostomin: Insights into protein scaffolds in integrin recognition
Protein Sci., 21:1872-1884, 2012

PubMed Abstract: 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 αIIbβ3 and 2.5 times less active when inhibiting the integrin αvβ3. In contrast, Den and Rho were similarly active when inhibiting the integrin α5β1 with the IC₅₀ 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 αvβ3 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.

PubMed: 23033223
DOI: 10.1002/pro.2169

実験手法

SOLUTION NMR