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

作者：Bahramali Golnaz; Goliaei Bahram; Minuchehr Zarrin; Marashi Sayed Amir

来源：Amino Acids, 2017, 49(2): 303-315.

DOI：10.1007/s00726-016-2361-6

• PPI networks
• Disease network
• Enrichment analysis
• Computational approaches

Chameleon proteins are proteins which include sequences that can adopt alpha-helix-beta-strand (HE- chameleon) or alpha-helix-coil (HC-chameleon) or beta-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.

• 出版日期2017-2