Deducing the functional characteristics of the human selenoprotein SELK from the structural properties of its intrinsically disordered C-terminal domain

摘要: The intrinsically disordered proteins (IDPs) cannot be described by a single structural representation but, due to their high fluctuation, through conformational ensembles. Certainly, molecular dynamics (MD) simulations represent useful tool study different conformations capturing the distribution. Our group is focusing on characterization of belonging seleno-proteome involvement in cancer. They present domains central for biological function, and, particular, SELK single-pass transmembrane protein that resides endoplasmic reticulum membrane (ER) with C-terminal domain exposed cytoplasm known interact components associated degradation (ERAD) pathway. This found up-expressed hepatocellular carcinoma and other cancers. In this work we performed detailed analysis sequence discovered it characterized many prolines, four negatively eleven positively charged residues, which are crucial its activity. region can considered as weak polyelectrolyte specifically, polycation, propensity phosphorylation sites dislocated along sequence. Then, modeled three-dimensional structure performing MD water at neutral pH analyze stability well identify presence HUB residues play key role evidenced residue-residue interaction network analysis. Through approach, demonstrate (i) presents poor content regular secondary elements, (ii) dynamically stabilized intra-molecular H-bonds molecules, (iii) highly fluctuating therefore, only ensemble, where distribution equilibrium conformers continuously inter-change conformations. Finally verify specific played negative charges, also acidic pH. Overall, all obtained results has dynamic features defined able multiple members. Therefore, considering possible have cancer development progression, target drug design studies.