https://orcid.org/0000-0003-4997-7173
![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
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.
Acknowledgements
We thank Professor Yupeng Chen, Professor Lei Shi, Professor Zhenyi Ma, Professor Wenyi Mi, and Professor Jie Yang from Tianjin Medical University for providing help with some experiments.
Disclosure statement
No potential conflict of interest was reported by the authors.
Data availability statement
All data needed to evaluate the conclusions in the paper are present in the paper and/or the supplementary materials. Additional data related to this paper may be requested from the authors.
Supplementary data
Supplemental data for this article can be accessed online at https://doi.org/10.1080/15548627.2023.2223468.