PDBsum entry: 1qag

Structural protein

PDB id: 1qag

Contents

Protein chains

226 a.a. *

Waters ×12

* Residue conservation analysis

PDB id:

1qag

Name:

Structural protein

Title:

Actin binding region of the dystrophin homologue utrophin

Structure:

Utrophin actin binding region. Chain: a, b. Fragment: residues 28-261. Engineered: yes. Mutation: yes. Other_details: the biological assembly is probably the mono than the dimer. This may be in an open configuration as the are in the crystal or in a closed configuration with the re 148 and b153-b256 in the crystal being formed by a single c

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

3.00Å R-factor: 0.198 R-free: 0.258

Authors:

N.H.Keep,S.J.Winder,C.A.Moores,S.Walke,F.L.M.Norwood,J.Kendr

Key ref:

N.H.Keep et al. (1999). Crystal structure of the actin-binding region of utrophin reveals a head-to-tail dimer. Structure, 7, 1539-1546. PubMed id: 10647184 DOI: 10.1016/S0969-2126(00)88344-6

Date:

05-Mar-99 Release date: 01-Jan-00

Protein chains

P46939  (UTRO_HUMAN) -  Utrophin

Seq: 3433 a.a.

Struc: 226 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 

• Biochemical function: protein binding (2 terms)

DOI no: 10.1016/S0969-2126(00)88344-6

Structure 7:1539-1546 (1999)

PubMed id: 10647184

Crystal structure of the actin-binding region of utrophin reveals a head-to-tail dimer.

N.H.Keep, S.J.Winder, C.A.Moores, S.Walke, F.L.Norwood, J.Kendrick-Jones.

ABSTRACT

BACKGROUND: Utrophin is a large multidomain protein that belongs to a superfamily of actin-binding proteins, which includes dystrophin, alpha-actinin, beta-spectrin, fimbrin, filamin and plectin. All the members of this family contain a common actin-binding region at their N termini and perform a wide variety of roles associated with the actin cytoskeleton. Utrophin is the autosomal homologue of dystrophin, the protein defective in the X-linked Duchenne and Becker muscular dystrophies, and upregulation of utrophin has been suggested as a potential therapy for muscular dystrophy patients. RESULTS: The structure of the actin-binding region of utrophin, consisting of two calponin-homology (CH) domains, has been solved at 3.0 A resolution. It is composed of an antiparallel dimer with each of the monomers being present in an extended dumbell shape and the two CH domains being separated by a long central helix. This extended conformation is in sharp contrast to the compact monomer structure of the N-terminal actin-binding region of fimbrin. CONCLUSIONS: The crystal structure of the actin-binding region of utrophin suggests that these actin-binding domains may be more flexible than was previously thought and that this flexibility may allow domain reorganisation and play a role in the actin-binding mechanism. Thus utrophin could possibly bind to actin in an extended conformation so that the sites previously identified as being important for actin binding may be directly involved in this interaction.

Selected figure(s)

Figure 2.
Figure 2. Similarity of CH domains of utrophin to other structures. (a) Stereo pair of superimposed a-carbon backbones for CH2 domains of utrophin (red), spectrin (blue) [17], fimbrin CH1.1 (purple) and fimbrin CH2.1 (green) [18], and utrophin CH1 (yellow). The utrophin sequence is numbered at every ten residues. The superpositions were calculated on helices a1, a3, a4 and a6 using LSQMAN [52]. (b) Stereo pair of the a-carbon backbone of the dimer structure shown in Figure 1a (rotated by 90° about the normal to the page); chain A is in red and chain B is in blue. Fimbrin (green) is superposed on the utrophin CH1 domain of A and CH2 domain of B. The red copy of the utrophin monomer is labelled every 20 residues. The figure was produced using BOBSCRIPT [51].

The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 1539-1546) copyright 1999.

Figure was selected by the author.