PDBsum entry 3tpo

Protein transport

PDB id: 3tpo

Contents

Protein chain

438 a.a.

Waters ×308

PDB id:

3tpo

Name:

Protein transport

Title:

Crystal structure of d192a/e396a mutant of mouse importin alpha2

Structure:

Importin subunit alpha-2. Chain: a. Synonym: importin alpha p1, karyopherin subunit alpha-2, pendulin, pore targeting complex 58 kda subunit, ptac58, rag cohort protein 1, srp1-alpha. Engineered: yes. Mutation: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: kpna2. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.10Å R-factor: 0.161 R-free: 0.192

Authors:

H.Hirano,Y.Matsuura

Key ref:

H.Hirano and Y.Matsuura (2011). Sensing actin dynamics: structural basis for G-actin-sensitive nuclear import of MAL. Biochem Biophys Res Commun, 414, 373-378. PubMed id: 21964294

Date:

08-Sep-11 Release date: 12-Oct-11

Protein chain

P52293  (IMA1_MOUSE) -  Importin subunit alpha-1 from Mus musculus

Seq: 529 a.a.

Struc: 438 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Biochem Biophys Res Commun 414:373-378 (2011)

PubMed id: 21964294

Sensing actin dynamics: structural basis for G-actin-sensitive nuclear import of MAL.

H.Hirano, Y.Matsuura.

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.