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PDBsum entry 1gkg
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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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Structure of the c3b binding site of cr1 (cd35), The immune adherence receptor.
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Authors
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B.O.Smith,
R.L.Mallin,
M.Krych-Goldberg,
X.Wang,
R.E.Hauhart,
K.Bromek,
D.Uhrin,
J.P.Atkinson,
P.N.Barlow.
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Ref.
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Cell, 2002,
108,
769-780.
[DOI no: ]
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PubMed id
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Abstract
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Complement receptor type 1 (CR1 or CD35) is a multiple modular protein that
mediates the immune adherence phenomenon, a fundamental event for destroying
microbes and initiating an immunological response. It fulfills this role through
binding C3b/C4b-opsonized foreign antigens. The structure of the principal
C3b/C4b binding site (residues 901-1095) of CR1 is reported, revealing three
complement control protein modules (modules 15-17) in an extended head-to-tail
arrangement with flexibility at the 16-17 junction. Structure-guided mutagenesis
identified a positively charged surface region on module 15 that is critical for
C4b binding. This patch, together with basic side chains of module 16 exposed on
the same face of CR1, is required for C3b binding. These studies reveal the
initial structural details of one of the first receptor-ligand interactions to
be identified in immunobiology.
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Figure 4.
Figure 4. Mutations Mapped onto Surface of Site 2Left:
surface of CR1  vert,
similar 15–17 using color scheme (red, 15; cyan, 16; blue,
17), except where mutagenesis yielded no significant loss of C3b
(iC3) binding or C4b binding (black), some loss of C3b (iC3)
binding (aa 937, 1053) or C4b binding (aa 927, 929, 1046)
(yellow), or major loss of C3b and/or C4b binding (white).
Single asterisk indicates residues that, when incorporated at
their equivalent positions in site 1 (i.e., D109N, N29K, and
T14K), caused gain of C3b binding. Double asterisk indicates two
residues (Y27S/G79D) that confer C3b binding activity when
simultaneously inserted at their equivalent positions in site
1.Right: same features but rotated (about vertical axis) by
180°.
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Figure 5.
Figure 5. Ligand Binding by Charge-Reverse Mutants in Site
2(A) iC3-Sepharose(B) C4b-SepharoseOne representative
measurement of two-to-four is shown by each data point. In the
case of C4b binding, mutants had binding values of ≤6%
compared to the parent fragment. Results are expressed as a
percentage of CR1 derivative bound to iC3-S or C4b-S of that
initially offered to the Sepharose.
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The above figures are
reprinted
by permission from Cell Press:
Cell
(2002,
108,
769-780)
copyright 2002.
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