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A network biology approach to understanding the importance of chameleon proteins in human physiology and pathology

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Abstract

Chameleon proteins are proteins which include sequences that can adopt α-helix–β-strand (HE-chameleon) or α-helix–coil (HC-chameleon) or β-strand–coil (CE-chameleon) structures to operate their crucial biological functions. In this study, using a network-based approach, we examined the chameleon proteins to give a better knowledge on these proteins. We focused on proteins with identical chameleon sequences with more than or equal to seven residues long in different PDB entries, which adopt HE-chameleon, HC-chameleon, and CE-chameleon structures in the same protein. One hundred and ninety-one human chameleon proteins were identified via our in-house program. Then, protein–protein interaction (PPI) networks, Gene ontology (GO) enrichment, disease network, and pathway enrichment analyses were performed for our derived data set. We discovered that there are chameleon sequences which reside in protein–protein interaction regions between two proteins critical for their dual function. Analysis of the PPI networks for chameleon proteins introduced five hub proteins, namely TP53, EGFR, HSP90AA1, PPARA, and HIF1A, which were presented in four PPI clusters. The outcomes demonstrate that the chameleon regions are in critical domains of these proteins and are important in the development and treatment of human cancers. The present report is the first network-based functional study of chameleon proteins using computational approaches and might provide a new perspective for understanding the mechanisms of diseases helping us in developing new medical therapies along with discovering new proteins with chameleon properties which are highly important in cancer.

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Acknowledgements

The authors would like to thank Nasibeh Khayyer for her valuable advice on the work. The work was done at the Bioinformatics Lab of the National Institute of Genetic Engineering and Biotechnology Grant No. 303 and at the Bioinformatics Group of University of Tehran.

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Authors and Affiliations

  1. Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

    Golnaz Bahramali & Bahram Goliaei

  2. Department of Systems Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran

    Zarrin Minuchehr

  3. Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran

    Sayed-Amir Marashi

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  1. Golnaz Bahramali
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Bahramali, G., Goliaei, B., Minuchehr, Z. et al. A network biology approach to understanding the importance of chameleon proteins in human physiology and pathology. Amino Acids 49, 303–315 (2017). https://doi.org/10.1007/s00726-016-2361-6

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