title: A network biology approach to understanding the importance of chameleon proteins in human physiology and pathology.
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.
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
authors.forename: Golnaz
authors.initials: G
authors.lastname: Bahramali
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran. goliaei@ut.ac.ir.
authors.forename: Bahram
authors.initials: B
authors.lastname: Goliaei
authors.affiliation: Department of Systems Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran. minuchehr@nigeb.ac.ir.
authors.forename: Zarrin
authors.identifier: http://orcid.org/0000-0002-3734-745X
authors.initials: Z
authors.lastname: Minuchehr
authors.affiliation: Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Sayed-Amir
authors.initials: SA
authors.lastname: Marashi
mesh_terms: D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D004194:Disease / Q000209:etiology; D006801:Humans; D001523:Mental Disorders / Q000378:metabolism; D011487:Protein Conformation; D060066:Protein Interaction Maps; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins
keywords: Computational approaches; Disease network; Enrichment analysis; PPI networks