2. Academic Validation
  3. HSPA8 regulates anti-bacterial autophagy through liquid-liquid phase separation

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

  • Autophagy. 2023 Jun 13;1-17. doi: 10.1080/15548627.2023.2223468.
Chunhui Miao 1,  Yajie Zhang 1,  Mingyu Yu 1,  Yuting Wei 1,  Cheng Dong 2,  Geng Pei 3,  Yawen Xiao 1,  Jianming Yang 1,  Zhi Yao 1,  Quan Wang 1
Affiliations

Affiliations

  • 1 Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Institute of Immunology, the Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Department of Immunology, School of Basic Medical Sciences, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
  • 2 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
  • 3 Department of Pathology, Tianjin Medical University Cancer Institute and Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
PMID: 37312409 DOI: 10.1080/15548627.2023.2223468
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 HSPA8 in modulating anti-bacterial Autophagy, and highlights the effect of LLPS-related HSPA8-RHOB-BECN1 complex on enhancing protein interaction and stabilization, which improves the understanding of autophagy-mediated defense against bacteria.

Keywords

Autophagy; HSPA8; LLPS; RHOB; bacteria.

Figures
Products