Complex Structures of an NTPase OsYchF1 Reveal the Working Mechanisms of the Ancestral YchF Subfamily G Proteins

XIAO-RONG LI, WEI WU, ZHONG-ZHOU CHEN

Abstract


G proteins are involved in almost all aspects of the cellular regulatory pathways through their ability to bind and hydrolyze GTP. The YchF subfamily are the core universally conserved G proteins and are present in all kingdoms of life. YchF proteins, interestingly, possess the unique ability to bind both ATP and GTP. However, the biological significance and working mechanism of such a highly conserved G proteins have long eluded researchers. Here, we have solved the structures of the apo forms of a YchF homolog in rice (OsYchF1) at four conditions and its complexes with ATP and GTP by using X-ray crystallography. These structures perfectly elucidate the conformational changes of OsYchF1 caused by different pH, ATP or GTP binding. Compared with other YchF homologs, OsYchF1 is the first YchF subfamily structure which completely displays three functional regions: G2/switch I, G3/switch II and Loop A. Furthermore, by comparing the conformational changes of the apo-OsYchF1 between weakly acidic and weakly alkaline conditions and of the ligand-bound versions, a working mechanism for the YchF protein’s ability to transduct signal is revealed. This discovery has a remarkable impact on our understanding of the structure-function relationships of the YchF subfamily of G proteins in all kingdoms of life. Human YchF homolog OLA1 is a multifunctional molecular switch-like ATPase and this regulatory ATPase is a potential novel target for antioxidative and antineoplastic therapy. Our results provide a structural basis to elucidate these molecular regulators, and may reveal novel insights into the understanding of cellular defense systems as well as expose new therapeutic targets for antioxidant and antineoplastic drugs.

Keywords


Small G proteins, YchF, Molecular basis, Complex structure.


DOI
10.12783/dtbh/icmsb2017/17949

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