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PDBsum entry 2arj
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Immune system
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PDB id
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2arj
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Contents |
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211 a.a.
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212 a.a.
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116 a.a.
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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 the tcr co-Receptor cd8alphaalpha in complex with monoclonal antibody yts 105.18 FAB fragment at 2.88 a resolution.
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Authors
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D.A.Shore,
L.Teyton,
R.A.Dwek,
P.M.Rudd,
I.A.Wilson.
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Ref.
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J Mol Biol, 2006,
358,
347-354.
[DOI no: ]
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PubMed id
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Abstract
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The CD8 glycoprotein functions as an essential element in the control of T-cell
selection, maturation and the TCR-mediated response to peptide antigen. CD8 is
expressed as both heterodimeric CD8alphabeta and homodimeric CD8alphaalpha
isoforms, which have distinct physiological roles and exhibit tissue-specific
expression patterns. CD8alphaalpha has previously been crystallized in complex
with class I pMHC and, more recently, with the mouse class Ib thymic leukemia
antigen (TL). Here, we present the crystal structure of a soluble form of mouse
CD8alphaalpha in complex with rat monoclonal antibody YTS 105.18 Fab fragment at
2.88 A resolution. YTS 105.18, which is commonly used in the blockade of CD8+
T-cell activation in response to peptide antigen, is specific for mouse
CD8alpha. The YTS 105.18 Fab is one of only five rat IgG Fab structures to have
been reported to date. Analysis of the YTS 105.18 Fab epitope on CD8alpha
reveals that this antibody blocks CD8 activity by hydrogen bonding to residues
that are critical for interaction with both class I pMHC and TL. Structural
comparison of the liganded and unliganded forms of soluble CD8alphaalpha
indicates that the mouse CD8alphaalpha immunoglobulin-domain dimer does not
undergo significant structural alteration upon interaction either with class I
pMHC or TL.
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Figure 1.
Figure 1. Mouse CD8aa complex with the YTS 105.18 Fab. (a)
Ribbon diagram of the refined model of the CD8aa/YTS 105.18 Fab
complex. Fab1 and Fab2 are in green and blue, respectively. The
CD8a1 and CD8a2 subunits are in maroon. (b) The epitope for the
YTS 105.18 Fab on the surface of the CD8aa subunit. YTS 105.18
binds the A, A' and B strands of CD8a. The epitope molecular
surface (grey) covered by YTS 105.18 is superimposed on the
ribbon diagram of CD8aa. Arg8 and Glu6 of CD8a, which are
involved in hydrogen bonding to class I pMHC, TL and also to YTS
105.18 Fab, are indicated. The single N-glycosylation site at
Asn42 within the CD8 construct is also indicated.
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Figure 3.
Figure 3. Comparison of CD8a interaction with YTS 105.18,
H-2Kb and TL. (a) Expanded view of the interface between CD8a
and YTS 105.18 Fab in stereo. The CD8aa/Fab complex is
orientated as in Figure 1(a), with CD8a1 (maroon) on the left
and YTS 105.18 Fab1 (blue) on the right. Hydrogen bonds are
indicated by a broken line. (b) Equivalent stereo view of the
interaction of CD8a1 (maroon) with class I pMHC (green), as
defined in the CD8aa/H-2Kb complex structure.18 (c) Equivalent
stereo view of the interaction between CD8a1 (maroon) and TL
(purple), as defined in the CD8aa/TL complex structure.19
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2006,
358,
347-354)
copyright 2006.
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