 |
PDBsum entry 2jcp
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Sugar binding protein
|
PDB id
|
|
|
|
2jcp
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structures of the cd44-Hyaluronan complex provide insight into a fundamental carbohydrate-Protein interaction.
|
|
|
Authors
|
|
S.Banerji,
A.J.Wright,
M.Noble,
D.J.Mahoney,
I.D.Campbell,
A.J.Day,
D.G.Jackson.
|
|
|
Ref.
|
|
Nat Struct Biol, 2007,
14,
234-239.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
perfect match.
|
|
|
|
Abstract
|
|
|
Regulation of transient interactions between cells and the ubiquitous matrix
glycosaminoglycan hyaluronan is crucial to such fundamental processes as
embryonic development and leukocyte homing. Cd44, the primary cell surface
receptor for hyaluronan, binds ligand via a lectin-like fold termed the Link
module, but only after appropriate functional activation. The molecular details
of the Cd44-hyaluronan interaction and hence the structural basis for this
activation are unknown. Here we present the first crystal structure of Cd44
complexed with hyaluronan. This reveals that the interaction with hyaluronan is
dominated by shape and hydrogen-bonding complementarity and identifies two
conformational forms of the receptor that differ in orientation of a crucial
hyaluronan-binding residue (Arg45, equivalent to Arg41 in human CD44).
Measurements by NMR indicate that the conformational transition can be induced
by hyaluronan binding, providing further insight into possible mechanisms for
regulation of Cd44.
|
|
|
|
|
|
|
|
Figure 1.
(a) Final refined 1.25-Å-resolution 2F[o] – F[c]
electron density for the binding site in the type A crystal
complex, calculated using SIGMAA^31 weighted map coefficients
generated by REFMAC^32 is contoured at 0.25 e^- Å^-3
(equivalent to the s.d. of the final map). Refined structure is
shown as sticks colored by atom type (green, Cd44 carbons; cyan,
HA carbons; blue, nitrogen; red, oxygen; yellow, sulfur).
Individual sugar rings in the bound HA[8] oligosaccharide are
numbered from the nonreducing end. (b) A ribbon diagram of mouse
Cd44 (type B complex), with secondary structure identified using
the DSSP algorithm^33. Pink,  -helices;
white, loops; green and gold,  -sheets
I and II, respectively; cyan, bound HA. (c) Surface
representation of the HA-binding site in the type B crystal
complex. The shallow HA-binding groove is shown as molecular
surface. Gold, supplementary lobe formed from N- and C-terminal
Link extensions; cyan, HA. Selected residues marking the
boundaries of the groove are labeled. The type A crystal form
shows similar features but lacks the lower platform for the HA
interaction provided by reorientation of Arg45.
|
|
Figure 2.
(a,b) The core of the HA-binding site (a) and the full
binding groove in the type B crystal complex (b) are shown as
sticks, colored as in Figure 1a. Dotted lines denote hydrogen
bonds (identified as contacts between polar atoms closer than
3.4 Å). Numbers indicate individual sugar rings, as in
Figure 1a.
|
|
|
|
|
|
The above figures are
reprinted
by permission from Macmillan Publishers Ltd:
Nat Struct Biol
(2007,
14,
234-239)
copyright 2007.
|
|
|
|
|
|
|
