HSP60: Protein Type

The HSP60/CPN60 family represents a group of well-conserved proteins with molecular weights ranging from 57 – 69 kDa. Functional genes encoding HSP60 proteins map to human chromosomes 1, 2, 5, 6, 7, 17, and 21. Hsp60 (also known as HspD1, Cpn60 or mitochondrial Hsp60) is a molecular chaperonin that assist protein folding in mitochondria ⁶⁶. In humans, Hsp60 is encoded by a nuclear gene (HSPD1) clustered on chromosome 2q33.1 and translated in the cytosol ⁶⁷. This gene is adjacent to a related family member, and the region between the two genes functions as a bidirectional promoter ⁶⁷. Several pseudogenes have been associated with this gene ⁶⁸. As the result of alternative splicing, two transcript variants encoding the same protein have been identified for the HSPD1 gene ⁶⁷. The corresponding protein consists of 573 amino acid residues and harbors a mitochondrial localization sequence (MLS) of 26 amino acids at the N-terminus necessary for its import into mitochondria ⁶⁹ as well as a series of G repeats at the C-terminus with unknown function ⁶³. Iterations of these repeats can also be found in several eukaryotic Hsp70 C-terminal sequences. Based on GroEL crystal structure data as well as sequence alignments of several Hsp60 sequences from different species, HSP60s have been found to contain highly conserved regions that may be involved in mediating Hsp60-specific functions ^{2, 49}. Intramitochondrial cleavage of the MLS generates the mature Hsp60 protein with 547 amino acids and a molecular mass of 61 kDa which is further processed by post-translational modifications. Like many other chaperones, Hsp60 is a phosphoprotein ⁷⁰ whose expression and function can be further modulated by suomylation ⁷¹, acetylation ⁷², malonylation ⁷³, N-glycosylation ⁷⁴ or O-GlcNAcylation ⁷⁵.