Research progress in the structures and functions of Gpn-loop GPN family proteins in Saccharomyces cerevisiae

Abstract:

Phosphate-binding loop nucleoside triphosphate hydrolase (P-loop NTPase) are a class of conserved proteins widely present in organisms, characterized by a conserved P-loop motif that is responsible for binding and hydrolyzing ATP or GTP. The GPN family (GPN-loop GTPase family) is a newly discovered subfamily of P-loop NTPase with GTP-hydrolyzing activity, characterized by a conserved glycine-proline-asparagine (GPN) motif. In eukaryotes, the GPN family includes three members: Gpn1, Gpn2, and Gpn3. Among them, Gpn1 (also known as Npa3) in Saccharomyces cerevisiae, a classic model organism, has been extensively studied. Homologs of Gpn2 (Yor262W) and Gpn3 (Ybr016W) are also present in the yeast genome. It is noteworthy that the GPN-loop domain is highly conserved throughout evolution and is essential, particularly in the assembly and nuclear transport of RNA polymerase Ⅱ (RNAP Ⅱ). Focusing on the S. cerevisiae model, this article systematically reviews the structural characteristics of the GPN family proteins and their molecular mechanisms of influencing transcription by regulating the assembly of RNAP Ⅱ and then explores the role of this family in cancer development. This review provides a theoretical reference for the analysis of eukaryotic transcriptional regulatory networks and new ideas for the development of therapeutic targets for related diseases.