| Structural highlights
Function
[GPN1_YEAST] Small GTPase required for proper nuclear import of RNA polymerase II (RNAPII) (PubMed:20855544, PubMed:21844196). May act at an RNAP assembly step prior to nuclear import (PubMed:23267056). Promotes sister chromatid separation during anaphase (PubMed:21532343).[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Biogenesis of the 12-subunit RNA polymerase II (Pol II) transcription complex requires so-called GPN-loop GTPases, but the function of these enzymes is unknown. Here we report the first crystal structure of a eukaryotic GPN-loop GTPase, the S. cerevisiae enzyme Npa3 (a homolog of human GPN1, also called RPAP4, XAB1, MBDin), and analyze its catalytic mechanism. The enzyme was trapped in a GDP-bound, closed conformation, and in a novel GTP analogue-bound, open conformation displaying a conserved hydrophobic pocket distant from the active site. We show that Npa3 has chaperone activity and interacts with hydrophobic peptide regions of Pol II subunits that form interfaces in the assembled Pol II complex. Biochemical results are consistent with a model that the hydrophobic pocket binds peptides, and that this can allosterically stimulate GTPase activity and subsequent peptide release. These results suggest that GPN-loop GTPases are assembly chaperones for Pol II and other protein complexes.
Structure of GPN-loop GTPase Npa3 and implications for RNA polymerase II assembly.,Niesser J, Wagner FR, Kostrewa D, Muhlbacher W, Cramer P Mol Cell Biol. 2015 Dec 28. pii: MCB.01009-15. PMID:26711263[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Keniry ME, Kemp HA, Rivers DM, Sprague GF Jr. The identification of Pcl1-interacting proteins that genetically interact with Cla4 may indicate a link between G1 progression and mitotic exit. Genetics. 2004 Mar;166(3):1177-86. PMID:15082539
- ↑ Forget D, Lacombe AA, Cloutier P, Al-Khoury R, Bouchard A, Lavallee-Adam M, Faubert D, Jeronimo C, Blanchette M, Coulombe B. The protein interaction network of the human transcription machinery reveals a role for the conserved GTPase RPAP4/GPN1 and microtubule assembly in nuclear import and biogenesis of RNA polymerase II. Mol Cell Proteomics. 2010 Dec;9(12):2827-39. doi: 10.1074/mcp.M110.003616. Epub, 2010 Sep 20. PMID:20855544 doi:https://dx.doi.org/10.1074/mcp.M110.003616
- ↑ Alonso B, Chaussinand G, Armengaud J, Godon C. A role for GPN-loop GTPase yGPN1 in sister chromatid cohesion. Cell Cycle. 2011 Jun 1;10(11):1828-37. Epub 2011 Jun 1. PMID:21532343
- ↑ Staresincic L, Walker J, Dirac-Svejstrup AB, Mitter R, Svejstrup JQ. GTP-dependent binding and nuclear transport of RNA polymerase II by Npa3 protein. J Biol Chem. 2011 Oct 14;286(41):35553-61. doi: 10.1074/jbc.M111.286161. Epub, 2011 Aug 15. PMID:21844196 doi:https://dx.doi.org/10.1074/jbc.M111.286161
- ↑ Minaker SW, Filiatrault MC, Ben-Aroya S, Hieter P, Stirling PC. Biogenesis of RNA polymerases II and III requires the conserved GPN small GTPases in Saccharomyces cerevisiae. Genetics. 2013 Mar;193(3):853-64. doi: 10.1534/genetics.112.148726. Epub 2012 Dec, 24. PMID:23267056 doi:https://dx.doi.org/10.1534/genetics.112.148726
- ↑ Niesser J, Wagner FR, Kostrewa D, Muhlbacher W, Cramer P. Structure of GPN-loop GTPase Npa3 and implications for RNA polymerase II assembly. Mol Cell Biol. 2015 Dec 28. pii: MCB.01009-15. PMID:26711263 doi:https://dx.doi.org/10.1128/MCB.01009-15
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