HSPA8 regulates anti-bacterial autophagy through liquid-liquid phase separation.

ABSTRACT: HSPA8 (heat shock protein family A (Hsp70) member 8) plays a significant role in the autophagic degradation of proteins, however, its effect on protein stabilization and anti-bacterial autophagy remains unknown. Here, it is discovered that HSPA8, as a binding partner of RHOB and BECN1, induce autophagy for intracellular bacteria clearance. Using its NBD and LID domains, HSPA8 physically binds to RHOB residues 1-42 and 89-118 as well as to BECN1 ECD domain, preventing RHOB and BECN1 degradation. Intriguingly, HSPA8 contains predicted intrinsically disordered regions (IDRs), and drives liquid-liquid phase separation (LLPS) to concentrate RHOB and BECN1 into HSPA8-formed liquid-phase droplets, resulting in improved RHOB and BECN1 interactions. Our study reveals a novel role and mechanism of H

SUBMITTER: Miao C 

PROVIDER: S-EPMC10472862 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature