1qbk

From Proteopedia

Revision as of 11:35, 20 March 2008

STRUCTURE OF THE KARYOPHERIN BETA2-RAN GPPNHP NUCLEAR TRANSPORT COMPLEX

Overview

Transport factors in the karyopherin-beta (also called importin-beta) family mediate the movement of macromolecules in nuclear-cytoplasmic transport pathways. Karyopherin-beta2 (transportin) binds a cognate import substrate and targets it to the nuclear pore complex. In the nucleus, Ran x GTP binds karyopherin-beta2 and dissociates the substrate. Here we present the 3.0 A structure of the karyopherin-beta2-Ran x GppNHp complex where GppNHp is a non-hydrolysable GTP analogue. Karyopherin-beta2 contains eighteen HEAT repeats arranged into two continuous orthogonal arches. Ran is clamped in the amino-terminal arch and substrate-binding activity is mapped to the carboxy-terminal arch. A large loop in HEAT repeat 7 spans both arches. Interactions of the loop with Ran and the C-terminal arch implicate it in GTPase-mediated dissociation of the import-substrate. Ran x GppNHp in the complex shows extensive structural rearrangement, compared to Ran GDP, in regions contacting karyopherin-beta2. This provides a structural basis for the specificity of the karyopherin-beta family for the GTP-bound state of Ran, as well as a rationale for interactions of the karyopherin-Ran complex with the regulatory proteins ranGAP, ranGEF and ranBP1.

Disease

Known diseases associated with this structure: Deafness, mitochondrial, modifier of OMIM:[610230], Osteolysis, familial expansile OMIM:[603499], Paget disease of bone OMIM:[603499]

About this Structure

1QBK is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structure of the nuclear transport complex karyopherin-beta2-Ran x GppNHp., Chook YM, Blobel G, Nature. 1999 May 20;399(6733):230-7. PMID:10353245

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