2V51

Structure of MAL-RPEL1 complexed to actin

PDB DOI: https://doi.org/10.2210/pdb2V51/pdb

Classification: STRUCTURAL PROTEIN/CONTRACTILE PROTEIN
Organism(s): Oryctolagus cuniculus, Mus musculus
Mutation(s): No

Deposited: 2008-10-01 Released: 2008-11-25
Deposition Author(s): Mouilleron, S., Guettler, S., Langer, C.A., Treisman, R., McDonald, N.Q.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.35 Å
R-Value Free: 0.248
R-Value Work: 0.183
R-Value Observed: 0.186

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Molecular basis for G-actin binding to RPEL motifs from the serum response factor coactivator MAL.

Mouilleron, S., Guettler, S., Langer, C.A., Treisman, R., McDonald, N.Q.

(2008) EMBO J 27: 3198-3208

PubMed: 19008859 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/emboj.2008.235
Primary Citation of Related Structures:
2V51, 2V52

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.

Organizational Affiliation

Structural Biology Laboratory, Cancer Research UK, London Research Institute, London, UK.

Macromolecule Content

Total Structure Weight: 94.09 kDa
Atom Count: 6,235
Modelled Residue Count: 759
Deposited Residue Count: 818
Unique protein chains: 2

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
ACTIN, ALPHA SKELETAL MUSCLE	A [auth B], B [auth D]	377	Oryctolagus cuniculus	Mutation(s): 0 EC: 3.6.4
UniProt
Find proteins for P68135 (Oryctolagus cuniculus) Explore P68135 Go to UniProtKB: P68135
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P68135
Sequence Annotations Expand
Reference Sequence

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(by identity cutoff) | 3D Structure

Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
MKL/MYOCARDIN-LIKE PROTEIN 1	C [auth E], D [auth F]	32	Mus musculus	Mutation(s): 0
UniProt
Find proteins for Q8K4J6 (Mus musculus) Explore Q8K4J6 Go to UniProtKB: Q8K4J6
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q8K4J6
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
ATP Query on ATP Download Ideal Coordinates CCD File SDF format, chain E [auth B] SDF format, chain K [auth D] MOL2 format, chain E [auth B] MOL2 format, chain K [auth D] mmCIF format, chain E [auth B] mmCIF format, chain K [auth D]	E [auth B], K [auth D]	ADENOSINE-5'-TRIPHOSPHATE C₁₀ H₁₆ N₅ O₁₃ P₃ ZKHQWZAMYRWXGA-KQYNXXCUSA-N		Interactions Focus chain E [auth B] Focus chain K [auth D] Interactions & Density Focus chain E [auth B] Focus chain K [auth D]
LAB Query on LAB Download Ideal Coordinates CCD File SDF format, chain G [auth B] SDF format, chain M [auth D] MOL2 format, chain G [auth B] MOL2 format, chain M [auth D] mmCIF format, chain G [auth B] mmCIF format, chain M [auth D]	G [auth B], M [auth D]	LATRUNCULIN B C₂₀ H₂₉ N O₅ S NSHPHXHGRHSMIK-JRIKCGFMSA-N		Interactions Focus chain G [auth B] Focus chain M [auth D] Interactions & Density Focus chain G [auth B] Focus chain M [auth D]
PEG Query on PEG Download Ideal Coordinates CCD File SDF format, chain H [auth B] SDF format, chain P [auth D] MOL2 format, chain H [auth B] MOL2 format, chain P [auth D] mmCIF format, chain H [auth B] mmCIF format, chain P [auth D]	H [auth B], P [auth D]	DI(HYDROXYETHYL)ETHER C₄ H₁₀ O₃ MTHSVFCYNBDYFN-UHFFFAOYSA-N		Interactions Focus chain H [auth B] Focus chain P [auth D] Interactions & Density Focus chain H [auth B] Focus chain P [auth D]
SCN Query on SCN Download Ideal Coordinates CCD File SDF format, chain I [auth B] SDF format, chain J [auth B] SDF format, chain N [auth D] SDF format, chain O [auth D] MOL2 format, chain I [auth B] MOL2 format, chain J [auth B] MOL2 format, chain N [auth D] MOL2 format, chain O [auth D] mmCIF format, chain I [auth B] mmCIF format, chain J [auth B] mmCIF format, chain N [auth D] mmCIF format, chain O [auth D]	I [auth B], J [auth B], N [auth D], O [auth D]	THIOCYANATE ION C N S ZMZDMBWJUHKJPS-UHFFFAOYSA-M		Interactions Focus chain I [auth B] Focus chain J [auth B] Focus chain N [auth D] Focus chain O [auth D] Interactions & Density Focus chain I [auth B] Focus chain J [auth B] Focus chain N [auth D] Focus chain O [auth D]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain F [auth B] SDF format, chain L [auth D] MOL2 format, chain F [auth B] MOL2 format, chain L [auth D] mmCIF format, chain F [auth B] mmCIF format, chain L [auth D]	F [auth B], L [auth D]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain F [auth B] Focus chain L [auth D] Interactions & Density Focus chain F [auth B] Focus chain L [auth D]

Binding Affinity Annotations
ID	Source	Binding Affinity
LAB	BindingDB: 2V51	IC50: 8470 (nM) from 1 assay(s)

Experimental Data & Validation

Experimental Data

Method: X-RAY DIFFRACTION
Resolution: 2.35 Å
R-Value Free: 0.248
R-Value Work: 0.183
R-Value Observed: 0.186
Space Group: P 1 2₁ 1

Unit Cell:

Length ( Å )	Angle ( ˚ )
a = 53.092	α = 90
b = 59.071	β = 90.06
c = 166.203	γ = 90

Software Package:

Software Name	Purpose
REFMAC	refinement
MOSFLM	data reduction
SCALA	data scaling
PHASER	phasing

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2008-11-25

Deposition Author(s):

Revision History (Full details and data files)

Version 1.0: 2008-11-25
Type: Initial release
Version 1.1: 2011-07-13
Changes: Advisory, Version format compliance
Version 1.2: 2018-02-28
Changes: Database references, Structure summary
Version 1.3: 2024-05-08
Changes: Data collection, Database references, Derived calculations, Other