5YFG

SOLUTION STRUCTURE OF HUMAN MOG1

Summary for 5YFG

• Entry DOI: 10.2210/pdb5yfg/pdb
• NMR Information: BMRB: 36117
• Descriptor: Ran guanine nucleotide release factor (1 entity in total)
• Functional Keywords: central beta sheet, alternative splicing, cytoplasm, guanine-nucleotide releasing factor, nucleus, protein transport
• Biological source: Homo sapiens (Human)
• Cellular location: Nucleus : Q9HD47
• Total number of polymer chains: 1
• Total formula weight: 21523.15

Authors

Hu, Q.,Liu, Y.,Bao, X.,Liu, H. (deposition date: 2017-09-21, release date: 2017-11-01, Last modification date: 2024-05-15)

Primary citation

Bao, X.,Liu, H.,Liu, X.,Ruan, K.,Zhang, Y.,Zhang, Z.,Hu, Q.,Liu, Y.,Akram, S.,Zhang, J.,Gong, Q.,Wang, W.,Yuan, X.,Li, J.,Zhao, L.,Dou, Z.,Tian, R.,Yao, X.,Wu, J.,Shi, Y.
Mitosis-specific acetylation tunes Ran effector binding for chromosome segregation
J Mol Cell Biol, 10:18-32, 2018

PubMed Abstract: Stable transmission of genetic information during cell division requires faithful mitotic spindle assembly and chromosome segregation. The Ran GTPase plays a key role in mitotic spindle assembly. However, how the generation of a chemical gradient of Ran-GTP at the spindle is coupled to mitotic post-translational modifications has never been characterized. Here, we solved the complex structure of Ran with the nucleotide release factor Mog1 and delineated a novel mitosis-specific acetylation-regulated Ran-Mog1 interaction during chromosome segregation. Our structure-guided functional analyses revealed that Mog1 competes with RCC1 for Ran binding in a GTP/GDP-dependent manner. Biochemical characterization demonstrated that Mog1-bound Ran prevents RCC1 binding and subsequent GTP loading. Surprisingly, Ran is a bona fide substrate of TIP60, and the acetylation of Lys134 by TIP60 liberates Mog1 from Ran binding during mitosis. Importantly, this acetylation-elicited switch of Ran binding to RCC1 promotes high level of Ran-GTP, which is essential for chromosome alignment. These results establish a previously uncharacterized regulatory mechanism in which TIP60 provides a homeostatic control of Ran-GTP level by tuning Ran effector binding for chromosome segregation in mitosis.

PubMed: 29040603
DOI: 10.1093/jmcb/mjx045

Experimental method

SOLUTION NMR