4HZK

Crystal structure of free CRM1 (crystal form 2)

Summary for 4HZK

• Entry DOI: 10.2210/pdb4hzk/pdb
• Descriptor: CRM1 Nuclear transport receptor (1 entity in total)
• Functional Keywords: heat repeat protein, nuclear export receptor, transport protein
• Biological source: Chaetomium thermophilum var. thermophilum
• Total number of polymer chains: 2
• Total formula weight: 249284.30

Authors

Monecke, T.,Neumann, P.,Dickmanns, A.,Ficner, R. (deposition date: 2012-11-15, release date: 2013-01-23, Last modification date: 2023-09-20)

Primary citation

Monecke, T.,Haselbach, D.,Voss, B.,Russek, A.,Neumann, P.,Thomson, E.,Hurt, E.,Zachariae, U.,Stark, H.,Grubmuller, H.,Dickmanns, A.,Ficner, R.
Structural basis for cooperativity of CRM1 export complex formation.
Proc.Natl.Acad.Sci.USA, 110:960-965, 2013

PubMed Abstract: In eukaryotes, the nucleocytoplasmic transport of macromolecules is mainly mediated by soluble nuclear transport receptors of the karyopherin-β superfamily termed importins and exportins. The highly versatile exportin chromosome region maintenance 1 (CRM1) is essential for nuclear depletion of numerous structurally and functionally unrelated protein and ribonucleoprotein cargoes. CRM1 has been shown to adopt a toroidal structure in several functional transport complexes and was thought to maintain this conformation throughout the entire nucleocytoplasmic transport cycle. We solved crystal structures of free CRM1 from the thermophilic eukaryote Chaetomium thermophilum. Surprisingly, unbound CRM1 exhibits an overall extended and pitched superhelical conformation. The two regulatory regions, namely the acidic loop and the C-terminal α-helix, are dramatically repositioned in free CRM1 in comparison with the ternary CRM1-Ran-Snurportin1 export complex. Single-particle EM analysis demonstrates that, in a noncrystalline environment, free CRM1 exists in equilibrium between extended, superhelical and compact, ring-like conformations. Molecular dynamics simulations show that the C-terminal helix plays an important role in regulating the transition from an extended to a compact conformation and reveal how the binding site for nuclear export signals of cargoes is modulated by different CRM1 conformations. Combining these results, we propose a model for the cooperativity of CRM1 export complex assembly involving the long-range allosteric communication between the distant binding sites of GTP-bound Ran and cargo.

PubMed: 23277578
DOI: 10.1073/pnas.1215214110

Experimental method

X-RAY DIFFRACTION (3.1 Å)