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.

Chameleon Sequences: Ordered or Disordered

“…Chameleon sequences have similar tendency to form helical, beta, or coil structures 3 .chameleon sequences include three categories of secondary structure transitions; helix to coil transition (HC), sheet to coil transition (EC), and helix to sheet transitions (HE) and vice versa. Chameleon sequences are responsible for many important functions of proteins, such as conserved protein folding and functional diversity in multiple splicing protein isoforms 4 , detection phenomena in immune system 5 and formation of many disease such as amyloid bril diseases 6,7 , and are important parameters in solving folding problems (sequence to structure relation). Chameleon sequences produce error in secondary structure prediction methods 8 Therefore, identi cation and characterization of these sequence is necessary for the correct modeling and prediction of protein secondary structure 9 .…”