1IQ1

CRYSTAL STRUCTURE OF THE IMPORTIN-ALPHA(44-54)-IMPORTIN-ALPHA(70-529) COMPLEX

Summary for 1IQ1

• Entry DOI: 10.2210/pdb1iq1/pdb
• Related: 1IAL
• Descriptor: IMPORTIN ALPHA-2 SUBUNIT (3 entities in total)
• Functional Keywords: armadillo repeat, solenoid, autoinhibition, protein transport
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cytoplasm (By similarity): P52293 P52293
• Total number of polymer chains: 3
• Total formula weight: 52615.74

Authors

Catimel, B.,Teh, T.,Fontes, M.R.M.,Jennings, I.G.,Kobe, B. (deposition date: 2001-05-28, release date: 2001-11-14, Last modification date: 2023-10-25)

Primary citation

Catimel, B.,Teh, T.,Fontes, M.R.,Jennings, I.G.,Jans, D.A.,Howlett, G.J.,Nice, E.C.,Kobe, B.
Biophysical characterization of interactions involving importin-alpha during nuclear import.
J.Biol.Chem., 276:34189-34198, 2001

PubMed Abstract: Proteins containing the classical nuclear localization sequences (NLSs) are imported into the nucleus by the importin-alpha/beta heterodimer. Importin-alpha contains the NLS binding site, whereas importin-beta mediates the translocation through the nuclear pore. We characterized the interactions involving importin-alpha during nuclear import using a combination of biophysical techniques (biosensor, crystallography, sedimentation equilibrium, electrophoresis, and circular dichroism). Importin-alpha is shown to exist in a monomeric autoinhibited state (association with NLSs undetectable by biosensor). Association with importin-beta (stoichiometry, 1:1; K(D) = 1.1 x 10(-8) m) increases the affinity for NLSs; the importin-alpha/beta complex binds representative monopartite NLS (simian virus 40 large T-antigen) and bipartite NLS (nucleoplasmin) with affinities (K(D) = 3.5 x 10(-8) m and 4.8 x 10(-8) m, respectively) comparable with those of a truncated importin-alpha lacking the autoinhibitory domain (T-antigen NLS, K(D) = 1.7 x 10(-8) m; nucleoplasmin NLS, K(D) = 1.4 x 10(-8) m). The autoinhibitory domain (as a separate peptide) binds the truncated importin-alpha, and the crystal structure of the complex resembles the structure of full-length importin-alpha. Our results support the model of regulation of nuclear import mediated by the intrasteric autoregulatory sequence of importin-alpha and provide a quantitative description of the binding and regulatory steps during nuclear import.

PubMed: 11448961
DOI: 10.1074/jbc.M103531200

Experimental method

X-RAY DIFFRACTION (2.8 Å)