X-ray structure of full-length human RuvB-Like 2 - mechanistic insights into coupling between ATP binding and mechanical action

Scientific Reports
Sara T N SilvaTiago M Bandeiras

Abstract

RuvB-Like transcription factors function in cell cycle regulation, development and human disease, such as cancer and heart hyperplasia. The mechanisms that regulate adenosine triphosphate (ATP)-dependent activity, oligomerization and post-translational modifications in this family of enzymes are yet unknown. We present the first crystallographic structure of full-length human RuvBL2 which provides novel insights into its mechanistic action and biology. The ring-shaped hexameric RuvBL2 structure presented here resolves for the first time the mobile domain II of the human protein, which is responsible for protein-protein interactions and ATPase activity regulation. Structural analysis suggests how ATP binding may lead to domain II motion through interactions with conserved N-terminal loop histidine residues. Furthermore, a comparison between hsRuvBL1 and 2 shows differences in surface charge distribution that may account for previously described differences in regulation. Analytical ultracentrifugation and cryo electron microscopy analyses performed on hsRuvBL2 highlight an oligomer plasticity that possibly reflects different physiological conformations of the protein in the cell, as well as that single-stranded DNA (ssDNA) can p...Continue Reading

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Citations

Apr 17, 2020·Biomolecules·Nardin NanoWalid A Houry
May 8, 2020·Science Translational Medicine·Dapeng JuEric Erquan Zhang
Nov 1, 2020·Current Opinion in Structural Biology·Maria I DaudenOscar Llorca
Apr 20, 2021·European Journal of Medicinal Chemistry·Gang ZhangTsui-Fen Chou

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Methods Mentioned

BETA
acetylation
X-ray
thermal shift
electrophoretic mobility shift assays
electrophoretic mobility shift assay
PCR
size exclusion purification

Software Mentioned

HYDROGENATE
COOT
CHARMM
CCP4
MolProbity
autoPROC
BUCCANEER
Scatter
TNT
PHASER

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