Journal Club Article

Journal Club Article - Human Cancer Protein-Protein...

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Human Cancer Protein-Protein Interaction Network: A Structural Perspective Gozde Kar, Attila Gursoy, Ozlem Keskin * Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Rumeli Feneri Yolu, Sariyer Istanbul, Turkey Abstract Protein-protein interaction networks provide a global picture of cellular function and biological processes. Some proteins act as hub proteins, highly connected to others, whereas some others have few interactions. The dysfunction of some interactions causes many diseases, including cancer. Proteins interact through their interfaces. Therefore, studying the interface properties of cancer-related proteins will help explain their role in the interaction networks. Similar or overlapping binding sites should be used repeatedly in single interface hub proteins, making them promiscuous. Alternatively, multi- interface hub proteins make use of several distinct binding sites to bind to different partners. We propose a methodology to integrate protein interfaces into cancer interaction networks (ciSPIN, cancer structural protein interface network). The interactions in the human protein interaction network are replaced by interfaces, coming from either known or predicted complexes. We provide a detailed analysis of cancer related human protein-protein interfaces and the topological properties of the cancer network. The results reveal that cancer-related proteins have smaller, more planar, more charged and less hydrophobic binding sites than non-cancer proteins, which may indicate low affinity and high specificity of the cancer-related interactions. We also classified the genes in ciSPIN according to phenotypes. Within phenotypes, for breast cancer, colorectal cancer and leukemia, interface properties were found to be discriminating from non-cancer interfaces with an accuracy of 71%, 67%, 61%, respectively. In addition, cancer-related proteins tend to interact with their partners through distinct interfaces, corresponding mostly to multi-interface hubs, which comprise 56% of cancer-related proteins, and constituting the nodes with higher essentiality in the network (76%). We illustrate the interface related affinity properties of two cancer-related hub proteins: Erbb3, a multi interface, and Raf1, a single interface hub. The results reveal that affinity of interactions of the multi-interface hub tends to be higher than that of the single-interface hub. These findings might be important in obtaining new targets in cancer as well as finding the details of specific binding regions of putative cancer drug candidates. Citation: Kar G, Gursoy A, Keskin O (2009) Human Cancer Protein-Protein Interaction Network: A Structural Perspective. PLoS Comput Biol 5(12): e1000601. doi:10.1371/journal.pcbi.1000601 Editor: Ruth Nussinov, National Cancer Institute, United States of America and Tel Aviv University, Israel Received June 3, 2009; Accepted November 5, 2009; Published December 11, 2009 Copyright: ß 2009 Kar et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
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Journal Club Article - Human Cancer Protein-Protein...

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