3TPM

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

Summary for 3TPM

• Entry DOI: 10.2210/pdb3tpm/pdb
• Related: 3TPO 3TPQ
• Descriptor: Importin subunit alpha-2, MAL (3 entities in total)
• Functional Keywords: nuclear import, protein transport-transcription complex, protein transport/transcription
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm (By similarity): P52293
• Total number of polymer chains: 2
• Total formula weight: 59856.77

Authors

Hirano, H.,Matsuura, Y. (deposition date: 2011-09-08, release date: 2011-10-12, Last modification date: 2023-11-01)

Primary citation

Hirano, H.,Matsuura, Y.
Sensing actin dynamics: structural basis for G-actin-sensitive nuclear import of MAL
Biochem.Biophys.Res.Commun., 414:373-378, 2011

PubMed Abstract: 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 α/β heterodimer, and that G-actin competes with importin α/β 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-α, 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-α- 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-α recognition.

PubMed: 21964294
DOI: 10.1016/j.bbrc.2011.09.079

Experimental method

X-RAY DIFFRACTION (2.1 Å)