3tpm

Crystal structure of MAL RPEL domain in complex with importin-alphaCrystal structure of MAL RPEL domain in complex with importin-alpha

Structural highlights 3tpm is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 3tpo, 3tpq Gene: Kpna2 (Mus musculus), Mkl1 (Mus musculus) Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The coordination of cytoskeletal actin dynamics with gene expression reprogramming is emerging as a crucial mechanism to control diverse cellular processes, including cell migration, differentiation and neuronal circuit assembly. The actin-binding transcriptional coactivator MAL (also known as MRTF-A/MKL1/BSAC) senses G-actin concentration and transduces Rho GTPase signals to serum response factor (SRF). MAL rapidly shuttles between the cytoplasm and the nucleus in unstimulated cells but Rho-induced depletion of G-actin leads to MAL nuclear accumulation and activation of transcription of SRF:MAL-target genes. Although the molecular and structural basis of actin-regulated nucleocytoplasmic shuttling of MAL is not understood fully, it is proposed that nuclear import of MAL is mediated by importin alpha/beta heterodimer, and that G-actin competes with importin alpha/beta for the binding to MAL. Here we present structural, biochemical and cell biological evidence that MAL has a classical bipartite nuclear localization signal (NLS) in the N-terminal 'RPEL' domain containing Arg-Pro-X-X-X-Glu-Leu (RPEL) motifs. The NLS residues of MAL adopt an extended conformation and bind along the surface groove of importin-alpha, interacting with the major- and minor-NLS binding sites. We also present a crystal structure of wild-type MAL RPEL domain in complex with five G-actins. Comparison of the importin-alpha- and actin-complexes revealed that the binding of G-actins to MAL is associated with folding of NLS residues into a helical conformation that is inappropriate for importin-alpha recognition. Sensing actin dynamics: structural basis for G-actin-sensitive nuclear import of MAL.,Hirano H, Matsuura Y Biochem Biophys Res Commun. 2011 Oct 22;414(2):373-8. doi:, 10.1016/j.bbrc.2011.09.079. Epub 2011 Sep 21. PMID:21964294 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Importin

spinqualitylabelsall models 3tpm, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image