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PDBsum entry 1ci5
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Immune system
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PDB id
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1ci5
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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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Functional glycan-Free adhesion domain of human cell surface receptor cd58: design, Production and nmr studies.
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Authors
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Z.Y.Sun,
V.Dötsch,
M.Kim,
J.Li,
E.L.Reinherz,
G.Wagner.
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Ref.
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EMBO J, 1999,
18,
2941-2949.
[DOI no: ]
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PubMed id
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Abstract
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A general strategy is presented here for producing glycan-free forms of
glycoproteins without loss of function by employing apolar-to-polar mutations of
surface residues in functionally irrelevant epitopes. The success of this
structure-based approach was demonstrated through the expression in Escherichia
coli of a soluble 11 kDa adhesion domain extracted from the heavily glycosylated
55 kDa human CD58 ectodomain. The solution structure was subsequently determined
and binding to its counter-receptor CD2 studied by NMR. This mutant adhesion
domain is functional as determined by several experimental methods, and the size
of its binding site has been probed by chemical shift perturbations in NMR
titration experiments. The new structural information supports a 'hand-shake'
model of CD2-CD58 interaction involving the GFCC'C" faces of both CD2 and
CD58 adhesion domains. The region responsible for binding specificity is most
likely localized on the C, C' and C" strands and the C-C' and C'-C"
loops on CD58.
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Figure 2.
Figure 2 Space-filling structural models for (A) a homology
model of the wild-type adhesion domain of CD58 depicting
surface-exposed hydrophobic residues and (B) the NMR structure
of 1dCD58[6m] depicting mutation sites. The molecules are viewed
edge-on, with  -strands
A and B directly in the front. Proline and glycine residues are
colored in yellow, other hydrophobic residues in green, mutation
sites in red, and putative glycan attachment positions in blue.
The graphs were prepared using GRASP (Nicholls et al., 1991).
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Figure 4.
Figure 4 Ribbon diagrams of (A) 1dCD58[6m], (B) homology model
of wild-type 1dCD58 and (C) NMR structure of the wild-type
adhesion domain of human CD2 (Withka et al., 1993; Bodian et
al., 1994; Wyss et al., 1995). The graphs were prepared using
MOLSCRIPT (Kraulis, 1991).
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
EMBO J
(1999,
18,
2941-2949)
copyright 1999.
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