 |
PDBsum entry 3ejh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cell adhesion
|
PDB id
|
|
|
|
3ejh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Identification and structural analysis of type i collagen sites in complex with fibronectin fragments.
|
|
|
Authors
|
|
M.C.Erat,
D.A.Slatter,
E.D.Lowe,
C.J.Millard,
R.W.Farndale,
I.D.Campbell,
I.Vakonakis.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 2009,
106,
4195-4200.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Collagen and fibronectin are major components of vertebrate extracellular
matrices. Their association and distribution control the development and
properties of diverse tissues, but thus far no structural information has been
available for the complex formed. Here, we report binding of a peptide, derived
from the alpha(1) chain of type I collagen, to the gelatin-binding domain of
human fibronectin and present the crystal structure of this peptide in complex
with the (8-9)FnI domain pair. Both gelatin-binding domain subfragments,
(6)FnI(1-2)FnII(7)FnI and (8-9)FnI, bind the same specific sequence on D-period
4 of collagen I alpha(1), adjacent to the MMP-1 cleavage site. (8-9)FnI also
binds the equivalent sequence of the alpha(2) chain. The collagen peptide adopts
an antiparallel beta-strand conformation, similar to structures of proteins from
pathogenic bacteria bound to FnI domains. Analysis of the type I collagen
sequence suggests multiple putative fibronectin-binding sites compatible with
our structural model. We demonstrate, by kinetic unfolding experiments, that the
triple-helical collagen state is destabilized by (8-9)FnI. This finding suggests
a role for fibronectin in collagen proteolysis and tissue remodeling.
|
|
|
|
|
|
|
|
Figure 3.
Overview of the complex structure. (A) Schematic
representation of the ^8–9FnI module pair in gold and the
α[1](I) G[778]–G[799] peptide in cyan showing the
antiparallel β-strand mode of binding. (B) Similar
representation of ^2–3FnI (purple) in complex with a peptide
(gold) from Staphylococcus aureus (21). Collagen and bacterial
peptides adopt a similar model of binding to FnI domains. (C)
Molecular surface area representation of ^8–9FnI colored by
electrostatic potential and select collagen peptides residues
involved in complex formation.
|
|
Figure 4.
Details from the molecular interaction of the complex. (A)
Hydrophobic interactions stabilizing the ^8–9FnI
(gold)–peptide (blue) conformation involve W[553] stacking
above the peptide (blue) plane and L[785] of α[1](I) contacting
H[539] and F[569]. (B) Stereoview of the β-stranded portion of
the collagen peptide. Two salt bridges to ^8–9FnI are formed
at its C terminus (green dashed lines) as well as important
hydrogen bonds among the residues shown. (C) Stereoview of the
peptide N terminus interacting with ^9FnI, primarily through
hydrogen bonds (red dashed lines).
|
|
|
|
|
|
|
|
|
|
