Systematic Identification and Competitive Disruption of Securin-Binding Partners in the Gene Diversity Space of Human Colorectal Cancer.

Human securin is regulatory protein involved in control of the metaphase-anaphase transition and anaphase onset of colorectal cancer. Molecular evidences suggest that the protein is integrated into oncogenic signaling network by binding to SH3-containing proteins through its proline-rich peptides. In this study, we have performed a genome-wide analysis and identification of securin-binding partners in the gene diversity space of human colorectal cancer. The securin-binding potency of SH3-containing proteins found in colorectal cancer was investigated by using bioinformatics modeling and intermolecular assay. With the protocol we were able to predict those high-affinity domain binders of the proline-rich peptides of human securin in a high-throughput manner, and to analyze sequence-specific interaction in the domain-peptide recognition at molecular level. Consequently, a number of putative domain binders with both high affinity and specificity were identified, from which the Src SH3 domain was selected as a case study and tested for its binding activity towards the securin peptides using fluorescence-based analysis. We also designed two peptide mutants that may have potent capability to competitively disrupt securin interaction with its partners. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Citation

Yinguang Zhang, Yongwang Zhang, Yuxiang Zhang. Systematic Identification and Competitive Disruption of Securin-Binding Partners in the Gene Diversity Space of Human Colorectal Cancer. Chemistry & biodiversity. 2017 May 06

PMID: 28477416

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