8JC5

Crystal structure of PLEKHM1 RUN domain in complex with GTP-bound Arl8b(Q75L)

8JC5 の概要

• エントリーDOI: 10.2210/pdb8jc5/pdb
• 分子名称: ADP-ribosylation factor-like protein 8B, Pleckstrin homology domain-containing family M member 1, GUANOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: plekhm1, run, arl8b, gtp-bound, gtpase, arf, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 83694.59

構造登録者

Qiu, X.H.,Pan, L.F. (登録日: 2023-05-10, 公開日: 2024-03-27)

主引用文献

Qiu, X.,Li, Y.,Wang, Y.,Gong, X.,Wang, Y.,Pan, L.
Mechanistic Insights into the Interactions of Arl8b with the RUN Domains of PLEKHM1 and SKIP.
J.Mol.Biol., 435:168293-168293, 2023

PubMed Abstract: Arl8b, a specific Arf-like family GTPase present on lysosome, and plays critical roles in many lysosome-related cellular processes such as autophagy. The active Arl8b can be specifically recognized by the RUN domains of two Arl8b-effectors PLEKHM1 and SKIP, thereby regulating the autophagosome/lysosome membrane fusion and the intracellular lysosome positioning, respectively. However, the mechanistic bases underlying the interactions of Arl8b with the RUN domains of PLEKHM1 and SKIP remain elusive. Here, we report the two high-resolution crystal structures of the active Arl8b in complex with the RUN domains of PLEKHM1 and SKIP. In addition to elucidating the detailed molecular mechanism governing the specific interactions of the active Arl8b with the RUN domains of PLEKHM1 and SKIP, the determined complex structures also reveal a general binding mode shared by the PLEKHM1 and SKIP RUN domains for interacting with the active Arl8b. Furthermore, we uncovered a competitive relationship between the RUN domains of PLEKHM1 and SKIP in binding to the active Arl8b as well as a unique small GTPase-binding mode adopted by the PLEKHM1 and SKIP RUN domains, thereby enriching the repertoire of the RUN domain/small GTPase interaction modes. In all, our findings provide new mechanistic insights into the interactions of the active Arl8b with PLEKHM1 and SKIP, and are valuable for further understanding the working modes of these proteins in relevant cellular processes.

PubMed: 37775038
DOI: 10.1016/j.jmb.2023.168293

実験手法

X-RAY DIFFRACTION (2.01 Å)