Dataset Information

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 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.

SUBMITTER: Cheng CH

PROVIDER: S-EPMC3575917 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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

Cheng Chun-Ho CH Chen Yi-Chun YC Shiu Jia-Hau JH Chang Yao-Tsung YT Chang Yung-Sheng YS Huang Chun-Hau CH Chen Chiu-Yueh CY Chuang Woei-Jer WJ

Protein science : a publication of the Protein Society 20121106 12

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 ...[more]

PMID: 23033223

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Project description:In recent years, the application of network analysis to neuroimaging data has provided useful insights about the brain's functional and structural organization in both health and disease. This has proven a significant paradigm shift from the study of individual brain regions in isolation. Graph-based models of the brain consist of vertices, which represent distinct brain areas, and edges which encode the presence (or absence) of a structural or functional relationship between each pair of vertices. By definition, any graph metric will be defined upon this dyadic representation of the brain activity. It is however unclear to what extent these dyadic relationships can capture the brain's complex functional architecture and the encoding of information in distributed networks. Moreover, because network representations of global brain activity are derived from measures that have a continuous response (i.e., interregional BOLD signals), it is methodologically complex to characterize the architecture of functional networks using traditional graph-based approaches. In the present study, we investigate the relationship between standard network metrics computed from dyadic interactions in a functional network, and a metric defined on the persistence homological scaffold of the network, which is a summary of the persistent homology structure of resting-state fMRI data. The persistence homological scaffold is a summary network that differs in important ways from the standard network representations of functional neuroimaging data: (i) it is constructed using the information from all edge weights comprised in the original network without applying an ad hoc threshold and (ii) as a summary of persistent homology, it considers the contributions of simplicial structures to the network organization rather than dyadic edge-vertices interactions. We investigated the information domain captured by the persistence homological scaffold by computing the strength of each node in the scaffold and comparing it to local graph metrics traditionally employed in neuroimaging studies. We conclude that the persistence scaffold enables the identification of network elements that may support the functional integration of information across distributed brain networks.

Dataset Information

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

Publications

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

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