PDBsum entry 4bsm

Protein transport

PDB id: 4bsm

Contents

Protein chain

896 a.a.

PDB id:

4bsm

Name:

Protein transport

Title:

Crystal structure of the nuclear export receptor crm1 (exportin-1) lacking thE C-terminal helical extension at 4.5a

Structure:

Exportin-1. Chain: a. Fragment: residues 1-1032. Synonym: human nuclear export receptor crm1, exp1, chromosome region maintenance 1 protein homolog, exportin1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

4.50Å R-factor: 0.233 R-free: 0.269

Authors:

C.Dian,F.Bernaudat,K.Langer,M.F.Oliva,M.Fornerod,G.Schoehn, C.W.Muller,C.Petosa

Key ref:

C.Dian et al. (2013). Structure of a truncation mutant of the nuclear export factor CRM1 provides insights into the auto-inhibitory role of its C-terminal helix. Structure, 21, 1338-1349. PubMed id: 23850454 DOI: 10.1016/j.str.2013.06.003

Date:

10-Jun-13 Release date: 31-Jul-13

Protein chain

O14980  (XPO1_HUMAN) -  Exportin-1 from Homo sapiens

Seq: 1071 a.a.

Struc: 896 a.a.*

* PDB and UniProt seqs differ at 20 residue positions (black crosses)

DOI no: 10.1016/j.str.2013.06.003

Structure 21:1338-1349 (2013)

PubMed id: 23850454

Structure of a truncation mutant of the nuclear export factor CRM1 provides insights into the auto-inhibitory role of its C-terminal helix.

C.Dian, F.Bernaudat, K.Langer, M.F.Oliva, M.Fornerod, G.Schoehn, C.W.Müller, C.Petosa.

ABSTRACT

Chromosome region maintenance 1/exportin1/Xpo1 (CRM1) associates with the GTPase Ran to mediate the nuclear export of proteins bearing a leucine-rich nuclear export signal (NES). CRM1 consists of helical hairpin HEAT repeats and a C-terminal helical extension (C-extension) that inhibits the binding of NES-bearing cargos. We report the crystal structure and small-angle X-ray scattering analysis of a human CRM1 mutant with enhanced NES-binding activity due to deletion of the C-extension. We show that loss of the C-extension leads to a repositioning of CRM1's C-terminal repeats and to a more extended overall conformation. Normal mode analysis predicts reduced rigidity for the deletion mutant, consistent with an observed decrease in thermal stability. Point mutations that destabilize the C-extension shift CRM1 to the more extended conformation, reduce thermal stability, and enhance NES-binding activity. These findings suggest that an important mechanism by which the C-extension regulates CRM1's cargo-binding affinity is by modulating the conformation and flexibility of its HEAT repeats.