1q1t

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Revision as of 22:11, 20 November 2007

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spinqualitylabelsall models 1q1t, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Mouse Importin alpha: non-phosphorylated SV40 CN peptide complex

Overview

The nuclear import of simian-virus-40 large T-antigen (tumour antigen) is, enhanced via phosphorylation by the protein kinase CK2 at Ser112 in the, vicinity of the NLS (nuclear localization sequence). To determine the, structural basis of the effect of the sequences flanking the basic cluster, KKKRK, and the effect of phosphorylation on the recognition of the NLS by, the nuclear import factor importin-alpha (Impalpha), we co-crystallized, non-autoinhibited Impalpha with peptides corresponding to the, phosphorylated and non-phosphorylated forms of the NLS, and determined the, crystal structures of the complexes. The structures show that the amino, acids N-terminally flanking the basic cluster make specific contacts with, the receptor that are distinct from the interactions between bipartite, NLSs and Impalpha. We confirm the important role of flanking sequences, using binding assays. Unexpectedly, the regions of the peptides containing, the phosphorylation site do not make specific contacts with the receptor., Binding assays confirm that phosphorylation does not increase the affinity, of the T-antigen NLS to Impalpha. We conclude that the sequences flanking, the basic clusters in NLSs play a crucial role in nuclear import by, modulating the recognition of the NLS by Impalpha, whereas phosphorylation, of the T-antigen enhances nuclear import by a mechanism that does not, involve a direct interaction of the phosphorylated residue with Impalpha.

About this Structure

1Q1T is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.

Reference

Role of flanking sequences and phosphorylation in the recognition of the simian-virus-40 large T-antigen nuclear localization sequences by importin-alpha., Fontes MR, Teh T, Toth G, John A, Pavo I, Jans DA, Kobe B, Biochem J. 2003 Oct 15;375(Pt 2):339-49. PMID:12852786

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