2V51

Structure of MAL-RPEL1 complexed to actin

Summary for 2V51

• Entry DOI: 10.2210/pdb2v51/pdb
• Related: 1ALM 1ATN 1EQY 1ESV 1H1V 1IJJ 1J6Z 1KXP 1LCU 1LOT 1M8Q 1MA9 1MVW 1NWK 1O18 1O19 1O1A 1O1B 1O1C 1O1D 1O1E 1O1F 1O1G 1P8Z 1QZ5 1QZ6 1RDW 1RFQ 1RGI 1S22 1SQK 1T44 1UY5 1WUA 1Y64 2A3Z 2A40 2A41 2A42 2A5X 2ASM 2ASO 2ASP 2D1K 2FF3 2FF6 2FXU 2V52 2VCP 2VYP
• Descriptor: ACTIN, ALPHA SKELETAL MUSCLE, MKL/MYOCARDIN-LIKE PROTEIN 1, ADENOSINE-5'-TRIPHOSPHATE, ... (8 entities in total)
• Functional Keywords: structural protein-contractile protein complex, contractile protein, structural protein, nucleotide-binding, transcription regulation, transcription, phosphoprotein, muscle protein, methylation, atp-binding, cytoskeleton, mal, rpel, actin, nucleus, structural protein/contractile protein
• Biological source: ORYCTOLAGUS CUNICULUS (RABBIT); More
• Cellular location: Cytoplasm, cytoskeleton: P68135; Cytoplasm: Q8K4J6
• Total number of polymer chains: 4
• Total formula weight: 94090.96

Authors

Mouilleron, S.,Guettler, S.,Langer, C.A.,Treisman, R.,McDonald, N.Q. (deposition date: 2008-10-01, release date: 2008-11-25, Last modification date: 2024-05-08)

Primary citation

Mouilleron, S.,Guettler, S.,Langer, C.A.,Treisman, R.,McDonald, N.Q.
Molecular basis for G-actin binding to RPEL motifs from the serum response factor coactivator MAL.
EMBO J., 27:3198-3208, 2008

PubMed Abstract: Serum response factor transcriptional activity is controlled through interactions with regulatory cofactors such as the coactivator MAL/MRTF-A (myocardin-related transcription factor A). MAL is itself regulated in vivo by changes in cellular actin dynamics, which alter its interaction with G-actin. The G-actin-sensing mechanism of MAL/MRTF-A resides in its N-terminal domain, which consists of three tandem RPEL repeats. We describe the first molecular insights into RPEL function obtained from structures of two independent RPEL(MAL) peptide:G-actin complexes. Both RPEL peptides bind to the G-actin hydrophobic cleft and to subdomain 3. These RPEL(MAL):G-actin structures explain the sequence conservation defining the RPEL motif, including the invariant arginine. Characterisation of the RPEL(MAL):G-actin interaction by fluorescence anisotropy and cell reporter-based assays validates the significance of actin-binding residues for proper MAL localisation and regulation in vivo. We identify important differences in G-actin engagement between the two RPEL(MAL) structures. Comparison with other actin-binding proteins reveals an unexpected similarity to the vitamin-D-binding protein, extending the G-actin-binding protein repertoire.

PubMed: 19008859
DOI: 10.1038/emboj.2008.235

Experimental method

X-RAY DIFFRACTION (2.35 Å)