6L6O

Crystal structure of stabilized Rab5a GTPase domain from Leishmania donovani

6L6O の概要

• エントリーDOI: 10.2210/pdb6l6o/pdb
• 分子名称: Rab5a, GUANOSINE-5'-DIPHOSPHATE, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: intracellular trafficking, gtpase, endocytosis
• 由来する生物種: Leishmania donovani
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20000.65

構造登録者

Arora, A.,Zohib, M.,Biswal, B.K.,Maheshwari, D.,Pal, R.K. (登録日: 2019-10-29, 公開日: 2020-11-11, 最終更新日: 2023-11-22)

主引用文献

Zohib, M.,Maheshwari, D.,Pal, R.K.,Freitag-Pohl, S.,Biswal, B.K.,Pohl, E.,Arora, A.
Crystal structure of the GDP-bound GTPase domain of Rab5a from Leishmania donovani.
Acta Crystallogr.,Sect.F, 76:544-556, 2020

PubMed Abstract: Eukaryotic Rab5s are highly conserved small GTPase-family proteins that are involved in the regulation of early endocytosis. Leishmania donovani Rab5a regulates the sorting of early endosomes that are involved in the uptake of essential nutrients through fluid-phase endocytosis. Here, the 1.80 Å resolution crystal structure of the N-terminal GTPase domain of L. donovani Rab5a in complex with GDP is presented. The crystal structure determination was enabled by the design of specific single-site mutations and two deletions that were made to stabilize the protein for previous NMR studies. The structure of LdRab5a shows the canonical GTPase fold, with a six-stranded central mixed β-sheet surrounded by five α-helices. The positions of the Switch I and Switch II loops confirm an open conformation, as expected in the absence of the γ-phosphate. However, in comparison to other GTP-bound and GDP-bound homologous proteins, the Switch I region traces a unique disposition in LdRab5a. One magnesium ion is bound to the protein at the GTP-binding site. Molecular-dynamics simulations indicate that the GDP-bound structure exhibits higher stability than the apo structure. The GDP-bound LdRab5a structure presented here will aid in efforts to unravel its interactions with its regulators, including the guanine nucleotide-exchange factor, and will lay the foundation for a structure-based search for specific inhibitors.

PubMed: 33135673
DOI: 10.1107/S2053230X20013722

実験手法

X-RAY DIFFRACTION (1.8 Å)