Imperial College London
Alternate

Prof Steve Matthews

Faculty of Natural Sciences, Department of Life Sciences

Professor of Chemical and Structural Biology
 
 
 
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Contact

 

+44 (0)20 7594 5315s.j.matthews Website

 
 
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Location

 

602Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Zhang:2022:10.1073/pnas.2116278119,
author = {Zhang, P and Zhao, X and Wang, Y and Du, K and Wang, Z and Yu, J and Chang, G and Matthews, S and Wang, H and Liu, B},
doi = {10.1073/pnas.2116278119},
journal = {Proc Natl Acad Sci U S A},
title = {Bacteriophage protein Gp46 is a cross-species inhibitor of nucleoid-associated HU proteins.},
url = {http://dx.doi.org/10.1073/pnas.2116278119},
volume = {119},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The architectural protein histone-like protein from Escherichia coli strain U93 (HU) is the most abundant bacterial DNA binding protein and highly conserved among bacteria and Apicomplexan parasites. It not only binds to double-stranded DNA (dsDNA) to maintain DNA stability but also, interacts with RNAs to regulate transcription and translation. Importantly, HU is essential to cell viability for many bacteria; hence, it is an important antibiotic target. Here, we report that Gp46 from bacteriophage SPO1 of Bacillus subtilis is an HU inhibitor whose expression prevents nucleoid segregation and causes filamentous morphology and growth defects in bacteria. We determined the solution structure of Gp46 and revealed a striking negatively charged surface. An NMR-derived structural model for the Gp46-HU complex shows that Gp46 occupies the DNA binding motif of the HU and therefore, occludes DNA binding, revealing a distinct strategy for HU inhibition. We identified the key residues responsible for the interaction that are conserved among HUs of bacteria and Apicomplexans, including clinically significant Mycobacterium tuberculosis, Acinetobacter baumannii, and Plasmodium falciparum, and confirm that Gp46 can also interact with these HUs. Our findings provide detailed insight into a mode of HU inhibition that provides a useful foundation for the development of antibacteria and antimalaria drugs.
AU  - Zhang,P
AU  - Zhao,X
AU  - Wang,Y
AU  - Du,K
AU  - Wang,Z
AU  - Yu,J
AU  - Chang,G
AU  - Matthews,S
AU  - Wang,H
AU  - Liu,B
DO  - 10.1073/pnas.2116278119
PY  - 2022///
TI  - Bacteriophage protein Gp46 is a cross-species inhibitor of nucleoid-associated HU proteins.
T2  - Proc Natl Acad Sci U S A
UR  - http://dx.doi.org/10.1073/pnas.2116278119
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35193978
VL  - 119
ER  -
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