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Updated: Jun 17, 2026
A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
Human cancer protein-protein interaction network: a structural perspective
Gozde Kar1, Attila Gursoy, Ozlem Keskin
1Center 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.
Insights
Cancer-related proteins have distinct interface properties, often acting as multi-interface hubs. This understanding aids in identifying new cancer targets and understanding drug interactions.
Area of Science:
- Biochemistry
- Bioinformatics
- Systems Biology
Background:
- Protein-protein interactions (PPIs) are crucial for cellular functions and biological processes.
- Dysfunctional PPIs are implicated in various diseases, notably cancer.
- Protein interfaces mediate these interactions, making their study vital for understanding disease mechanisms.
Purpose of the Study:
- To develop a methodology integrating protein interfaces into cancer interaction networks (ciSPIN).
- To analyze the properties of cancer-related protein interfaces and their network topology.
- To identify potential biomarkers and therapeutic targets in cancer.
Main Methods:
- Integration of known or predicted protein complexes into the human protein interaction network to form the cancer structural protein interface network (ciSPIN).
- Analysis of topological properties and interface characteristics of cancer-related proteins within ciSPIN.
- Classification of genes by phenotypes and comparison of interface properties between cancer and non-cancer proteins.
Main Results:
- Cancer-related protein interfaces are generally smaller, more planar, more charged, and less hydrophobic than those of non-cancer proteins.
- Interface properties can discriminate cancer-related proteins from non-cancer proteins with significant accuracy (e.g., 71% for breast cancer).
- Cancer-related proteins predominantly function as multi-interface hubs (56%), indicating essentiality in the network (76%).
Conclusions:
- Cancer-related protein interfaces exhibit unique biophysical properties suggesting specific interaction dynamics.
- Multi-interface hubs are prevalent among cancer proteins and are critical network nodes.
- These findings offer insights into cancer mechanisms and potential avenues for novel therapeutic strategies.
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