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PDBsum entry 1fnh
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Heparin and integrin binding
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PDB id
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1fnh
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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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Crystal structure of a heparin- And integrin-Binding segment of human fibronectin.
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Authors
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A.Sharma,
J.A.Askari,
M.J.Humphries,
E.Y.Jones,
D.I.Stuart.
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Ref.
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EMBO J, 1999,
18,
1468-1479.
[DOI no: ]
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PubMed id
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Abstract
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The crystal structure of human fibronectin (FN) type III repeats 12-14 reveals
the primary heparin-binding site, a clump of positively charged residues in
FN13, and a putative minor site approximately 60 A away in FN14. The IDAPS motif
implicated in integrin alpha4beta1 binding is at the FN13-14 junction, rendering
the critical Asp184 inaccessible to integrin. Asp184 clamps the BC loop of FN14,
whose sequence (PRARI) is reminiscent of the synergy sequence (PHSRN) of FN9.
Mutagenesis studies prompted by this observation reveal that both arginines of
the PRARI sequence are important for alpha4beta1 binding to FN12-14. The PRARI
motif may represent a new class of integrin-binding sites. The spatial
organization of the binding sites suggests that heparin and integrin may bind in
concert.
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Figure 1.
Figure 1 (A) The modular architecture of human FN showing the
type I, II and III repeats and the known binding sites for
various ligands. Boxes in green and blue correspond to regions
where structural information is available (Williams et al.,
1994; Leahy et al., 1996; Sticht et al., 1998). (B) A
structure-based sequence alignment of 17 type III human FN
repeats. Secondary structure classification is based on all
repeats in FN12–14; FNEDA and FNEDB denotes the extra repeats
A and B. Residues in green are identical in all 17 repeats, in
aquamarine are identical in at least 12 repeats, and in yellow
identical in 8–11 repeats. Residues in red are implicated in
integrin binding. The first nine residues of FN15 (shaded) are
part of IIICS (see text). All molecular graphic figures are
generated using BOBSCRIPT (Esnouf, 1997) and RASTER3D (Merritt
and Murphy, 1994), or GRASP (Nicholls et al., 1991).
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Figure 2.
Figure 2 Orthogonal views of FN12–14 structure. The structure
is represented as a cartoon with the  -strands
(defined by inspection) shown as arrows. The chain is coloured
from blue to green to red as the polypeptide goes from the N- to
the C-terminus. The repeats correspond to FN12, FN13 and FN14.
Individual strands are labelled in one repeat in each case.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(1999,
18,
1468-1479)
copyright 1999.
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