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PDBsum entry 1u5m
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Structural protein
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PDB id
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1u5m
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Solution structure and dynamics of a prototypical chordin-Like cysteine-Rich repeat (von willebrand factor type c module) from collagen iia.
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Authors
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J.M.O'Leary,
J.M.Hamilton,
C.M.Deane,
N.V.Valeyev,
L.J.Sandell,
A.K.Downing.
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Ref.
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J Biol Chem, 2004,
279,
53857-53866.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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).
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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.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2004,
279,
53857-53866)
copyright 2004.
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Secondary reference #1
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Title
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Identification and removal of o-Linked and non-Covalently linked sugars from recombinant protein produced using pichia pastoris
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Authors
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J.M.O'Leary,
C.M.Radcliffe,
A.C.Willis,
R.A.Dwek,
P.M.Rudd,
A.K.Downing.
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Ref.
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protein expr purif ...
[DOI no: ]
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PubMed id
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