Dynamics and functional differences between dendroaspin and rhodostomin: Insights into protein scaffolds in integrin recognition

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 KI 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 IC50values 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. Published by Wiley-Blackwell.

Original languageEnglish
Pages (from-to)1872-1884
Number of pages13
JournalProtein Science
Volume21
Issue number12
DOIs
Publication statusPublished - 2012 Dec 1

Fingerprint

Scaffolds
Integrins
Proteins
mambin
rhodostomin
Snake Venoms
Pichia
Cell adhesion
Platelets
Platelet Aggregation
Cell Adhesion
Conformations
Agglomeration
Nuclear magnetic resonance

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

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title = "Dynamics and functional differences between dendroaspin and rhodostomin: Insights into protein scaffolds in integrin recognition",
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 KI 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 IC50values 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. Published by Wiley-Blackwell.",
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Dynamics and functional differences between dendroaspin and rhodostomin : Insights into protein scaffolds in integrin recognition. / Cheng, Chun Ho; Chen, Yi Chun; Shiu, Jia Hau; Chang, Yao Tsung; Chang, Yung Sheng; Huang, Chun Hau; Chen, Chiu Yueh; Chuang, Woei Jer.

In: Protein Science, Vol. 21, No. 12, 01.12.2012, p. 1872-1884.

Research output: Contribution to journalArticle

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T2 - Insights into protein scaffolds in integrin recognition

AU - Cheng, Chun Ho

AU - Chen, Yi Chun

AU - Shiu, Jia Hau

AU - Chang, Yao Tsung

AU - Chang, Yung Sheng

AU - Huang, Chun Hau

AU - Chen, Chiu Yueh

AU - Chuang, Woei Jer

PY - 2012/12/1

Y1 - 2012/12/1

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