Structural insights into the formation of oligomeric state by a type I Hsp40 chaperone

• Published in: Biochimie 2020-09, Vol.176, p.45-51
• Main Authors: Zhu, Min, Ou, Dingmin, Khan, Muhammad Hidayatullah, Zhao, Shasha, Zhu, Zhongliang, Niu, Liwen
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - chemistry; Chaperones; Crystal structure; Crystallography, X-Ray; Dimer; Dynamic multivalent interaction; Heat shock proteins; HSP40 Heat-Shock Proteins - chemistry; HSP70 Heat-Shock Proteins - chemistry; Oligomer; Protein Domains; Protein Multimerization; Protein Structure, Quaternary; Streptococcus pneumoniae - chemistry
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2020.06.009

Molecular chaperones can prevent and repair protein misfolding and aggregation to maintain protein homeostasis in cells. Hsp40 chaperones interact with unfolded client proteins via the dynamic multivalent interaction (DMI) mechanism with their multiple client-binding sites. Here we report that a type I Hsp40 chaperone from Streptococcus pneumonia (spHsp40) forms a concentration-independent polydispersity oligomer state in solution. The crystal structure of spHsp40 determined at 2.75 Å revealed that each monomer has a type I Hsp40 structural fold containing a zinc finger domain and C-terminal domains I and II (CTD I and CTD II). Subsequent quaternary structure analysis using a PISA server generated two dimeric models. The interface mutational analysis suggests the conserved C-terminal dimeric motif as a basis for dimer formation and that the novel dimeric interaction between a client-binding site in CTD I and the zinc finger domain promotes the formation of the spHsp40 oligomeric state. In vitro functional analysis demonstrated that spHsp40 oligomer is fully active and possess the optimal activity in stimulating the ATPase activity of spHsp70. The oligomer state of type I Hsp40 and its formation might be important in understanding Hsp40 function and its interaction with client proteins. •Structure model of spHsp40 reveals two dimeric interfaces.•Interface mutations convert spHsp40 from oligomer to dimer and monomer.•The β3 in zinc finger of spHsp40 have a weak interaction with hydrophobic pocket in CTD I domain.•The oligomeric spHsp40 is fully active and has the optimal activity in stimulating the ATPase activity of spHsp70.