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PDBsum entry 2w86
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References listed in PDB file
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Key reference
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Title
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Structure and interdomain interactions of a hybrid domain: a disulphide-Rich module of the fibrillin/ltbp superfamily of matrix proteins.
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Authors
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S.A.Jensen,
S.Iqbal,
E.D.Lowe,
C.Redfield,
P.A.Handford.
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Ref.
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Structure, 2009,
17,
759-768.
[DOI no: ]
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PubMed id
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Abstract
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The fibrillins and latent transforming growth factor-beta binding proteins
(LTBPs) form a superfamily of structurally-related proteins consisting of
calcium-binding epidermal growth factor-like (cbEGF) domains interspersed with
8-cysteine-containing transforming growth factor beta-binding protein-like (TB)
and hybrid (hyb) domains. Fibrillins are the major components of the
extracellular 10-12 nm diameter microfibrils, which mediate a variety of
cell-matrix interactions. Here we present the crystal structure of a fibrillin-1
cbEGF9-hyb2-cbEGF10 fragment, solved to 1.8 A resolution. The hybrid domain fold
is similar, but not identical, to the TB domain fold seen in previous
fibrillin-1 and LTBP-1 fragments. Pairwise interactions with neighboring cbEGF
domains demonstrate extensive interfaces, with the hyb2-cbEGF10 interface
dependent on Ca(2+) binding. These observations provide accurate constraints for
models of fibrillin organization within the 10-12 nm microfibrils and provide
further molecular insights into how Ca(2+) binding influences the intermolecular
interactions and biomechanical properties of fibrillin-1.
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Figure 1.
Figure 1. Domain Organization of Human Fibrillin-1
The
fibrillin sequence is largely dominated by cbEGF domains,
interspersed with TB and hyb domains. Constructs used to
determine Ca^2+ affinities of hyb-cbEGF pairs and the
cbEGF9-hyb2-cbEGF10 construct are shown above the figure.
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Figure 4.
Figure 4. Residues Involved in the Formation of Interdomain
Interfaces
(A and B) Residues involved in interdomain
contacts were identified using the program Contact in the CCP4
program suite (CCP4, 1994), with a distance limit of 4 Å.
Hyb domain residues at the cbEGF9-hyb2 interface (A) or
hyb2-cbEGF10 interface (B) are indicated by magenta spheres and
interacting cbEGF residues are indicated by green spheres.
(C) An alignment of the hyb2 and TB4 domains shows similarities
of the regions involved in interactions with either the
N-terminal (red) or C-terminal (cyan) cbEGFs. Domains were
aligned using Clustal W 2.0 (Larkin et al., 2007), and cysteines
are highlighted in yellow.
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The above figures are
reprinted
from an Open Access publication published by Cell Press:
Structure
(2009,
17,
759-768)
copyright 2009.
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