PDBsum entry 1u5m

Structural protein

PDB id: 1u5m

Contents

Protein chain

73 a.a. *

* Residue conservation analysis

PDB id:

1u5m

Name:

Structural protein

Title:

Structure of a chordin-like cysteine-rich repeat (vwc module) from collagen iia

Structure:

Alpha 1 type ii collagen isoform 1. Chain: a. Fragment: exon2. Synonym: collagen ii, alpha-1 polypeptide. Cartilage collagen. Chondrocalcin, included. Col11a3, formerly. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: col2a1. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

NMR struc:

20 models

Authors:

J.M.O'Leary,J.M.Hamilton,C.M.Deane,N.V.Valeyev,L.J.Sandell, A.K.Downing

Key ref:

J.M.O'Leary et al. (2004). Solution structure and dynamics of a prototypical chordin-like cysteine-rich repeat (von Willebrand Factor type C module) from collagen IIA. J Biol Chem, 279, 53857-53866. PubMed id: 15466413 DOI: 10.1074/jbc.M409225200

Date:

28-Jul-04 Release date: 05-Oct-04

Protein chain

P02458  (CO2A1_HUMAN) -  Collagen alpha-1(II) chain from Homo sapiens

Seq: 1487 a.a.

Struc: 73 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1074/jbc.M409225200

J Biol Chem 279:53857-53866 (2004)

PubMed id: 15466413

Solution structure and dynamics of a prototypical chordin-like cysteine-rich repeat (von Willebrand Factor type C module) from collagen IIA.

J.M.O'Leary, J.M.Hamilton, C.M.Deane, N.V.Valeyev, L.J.Sandell, A.K.Downing.

ABSTRACT

Chordin-like cysteine-rich (CR) repeats (also referred to as von Willebrand factor type C (VWC) modules) have been identified in approximately 200 extracellular matrix proteins. These repeats, named on the basis of amino acid conservation of 10 cysteine residues, have been shown to bind members of the transforming growth factor-beta (TGF-beta) superfamily and are proposed to regulate growth factor signaling. Here we describe the intramolecular disulfide bonding, solution structure, and dynamics of a prototypical chordin-like CR repeat from procollagen IIA (CR(ColIIA)), which has been previously shown to bind TGF-beta1 and bone morphogenetic protein-2. The CR(ColIIA) structure manifests a two sub-domain architecture tethered by a flexible linkage. Initial structures were calculated using RosettaNMR, a de novo prediction method, and final structure calculations were performed using CANDID within CYANA. The N-terminal region contains mainly beta-sheet and the C-terminal region is more irregular with the fold constrained by disulfide bonds. Mobility between the N- and C-terminal sub-domains on a fast timescale was confirmed using NMR relaxation measurements. We speculate that the mobility between the two sub-domains may decrease upon ligand binding. Structure and sequence comparisons have revealed an evolutionary relationship between the N-terminal sub-domain of the CR module and the fibronectin type 1 domain, suggesting that these domains share a common ancestry. Based on the previously reported mapping of fibronectin binding sites for vascular endothelial growth factor to regions containing fibronectin type 1 domains, we discuss the possibility that this structural homology might also have functional relevance.

Selected figure(s)

Figure 1.
FIG. 1. Multiple sequence alignment of CR repeat sequences from the SWISS-PROT data base from procollagen IIA, chordin, connective tissue growth factor, neuralin, and Cyr61. Residues Cys34-Cys89 of the CR[ColIIA] sequence, corresponding to the Pfam entry for the VWC domain, are shown. Sequences were aligned using ClustalX (71).

Figure 5.
FIG. 5. Comparison of the N-terminal sub-domain of CR[ColIIA] (shown in turquoise) and fibronectin type 1 (shown in pink) domains. A, structural alignment of the N-terminal domain of CR[CoIIIA] and the N-terminal domain of 1FBR (a representative structure of the fibronectin type 1 domain) based on the backbone atoms of 40 residues (r.m.s.d. = 2.0 Å). Cysteines in the N-terminal domain of CR[CoIIIA] domain are highlighted in black excluding Cys52, which is not conserved in fibronectin domains but forms a disulfide bond to the second domain in CR[CoIIIA]. B, multiple sequence alignment of the N-terminal sub-domain of CR[ColIIA] and FN1 domain sequences from fibronectin. For the CR[ColIIA] sequence, residues Ala^31-Ile^67 are shown in the alignment.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 53857-53866) copyright 2004.

Figures were selected by an automated process.