Liquid-liquid phase separation of functional proteins and its implication

Abstract

The main soluble protein component of the circulatory system, serum albumins, serves various physiological purposes [1]. The ability of this class of proteins to act as transporters for many substances is their most significant characteristic. BSA has undergone some of the most in-depth research within this class of proteins, in part due to the structural similarities between BSA (isolated from cow) and human serum albumin (HSA) [2]. Both albumins have identical binding sites on subdomains IIA and IIIA and have a 76% sequence homology. The amino acids lining the binding sites are primarily hydrophobic [3]. HSA comprises a solitary polypeptide chain with a molecular weight of approximately 66 kDa and around 585 amino acids. The HSA molecule is structured into three homologous domains (I, II, III), which are further subdivided into nine loops (L1-L9) through the presence of 17 disulfide linkages [4]. (Figure 1a) shows the three-dimensional structure of HSA (The Crystal Structure of HSA (PDB Entry 7DJN; obtained from protein data bank). Several proteins having low-complexity domains (LCDs) in their amino acid sequence and intrinsically disordered regions (IDRs) have recently been found to conduct LLPS in the presence or absence of inert macromolecular crowders [5].