RGD Reference Report - Crystallographic and biochemical analysis of the Ran-binding zinc finger domain. - Rat Genome Database

RGD Reference Report - Crystallographic and biochemical analysis of the Ran-binding zinc finger domain. - Rat Genome Database

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General

Crystallographic and biochemical analysis of the Ran-binding zinc finger domain.
Authors:	Partridge, JR Schwartz, TU
Citation:	Partridge JR and Schwartz TU, J Mol Biol. 2009 Aug 14;391(2):375-89. Epub 2009 Jun 6.
RGD ID:	4145659
Pubmed:	PMID:19505478 (View Abstract at PubMed)
PMCID:	PMC2716403 (View Article at PubMed Central)
DOI:	DOI:10.1016/j.jmb.2009.06.011 (Journal Full-text)
The nuclear pore complex (NPC) resides in circular openings within the nuclear envelope and serves as the sole conduit to facilitate nucleocytoplasmic transport in eukaryotes. The asymmetric distribution of the small G protein Ran across the nuclear envelope regulates directionality of protein transport. Ran interacts with the NPC of metazoa via two asymmetrically localized components, Nup153 at the nuclear face and Nup358 at the cytoplasmic face. Both nucleoporins contain a stretch of distinct, Ran-binding zinc finger domains. Here, we present six crystal structures of Nup153-zinc fingers in complex with Ran and a 1.48 A crystal structure of RanGDP. Crystal engineering allowed us to obtain well diffracting crystals so that all ZnF-Ran complex structures are refined to high resolution. Each of the four zinc finger modules of Nup153 binds one Ran molecule in apparently non-allosteric fashion. The affinity is measurably higher for RanGDP than for RanGTP and varies modestly between the individual zinc fingers. By microcalorimetric and mutational analysis, we determined that one specific hydrogen bond accounts for most of the differences in the binding affinity of individual zinc fingers. Genomic analysis reveals that only in animals do NPCs contain Ran-binding zinc fingers. We speculate that these organisms evolved a mechanism to maintain a high local concentration of Ran at the vicinity of the NPC, using this zinc finger domain as a sink.

Cellular Component

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Nup153	Rat	protein-containing complex		IDA			RGD
Ran	Rat	protein-containing complex		IDA			RGD

Molecular Function

Only show annotations with direct experimental evidence (0 objects hidden)

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Ran	Rat	GDP binding		IDA			RGD
Ran	Rat	GTP binding		IDA			RGD
Ran	Rat	protein domain specific binding		IPI	Nup153 (Rattus norvegicus)		RGD
Nup153	Rat	small GTPase binding		IPI	Ran (Rattus norvegicus)		RGD
Nup153	Rat	zinc ion binding		IDA			RGD

Genes (Rattus norvegicus)


Nup153 (nucleoporin 153)	Ran (RAN, member RAS oncogene family)