Role of the transmembrane polar residues on CD151 in cholesterol binding

Tetraspanins superfamily proteins have been shown to play an important role in several physiological processes and diseases such as cancer. Transmembrane polar residues of tetraspanins have an implication in regulating the process of cancer metastasis. Tetraspanin CD82 has been demonstrated to exert an anti-metastatic role while mutating polar residues in its transmembrane domains (TMDs) abrogates its metastasis inhibitory role. However, CD151, being pro-metastatic tetraspanin, the role of polar residues in TMDs of CD151 in cholesterol binding and its stability has not been investigated. In this study, we employed bioinformatics analysis of CD151 sequences to determine polar residue in TMDs, molecular docking, dynamics, and normal mode analysis studies to investigate the contribution of polar residues on cholesterol binding by modelling and comparing wild type with polar residue mutant of CD151. The study finds three polar residues