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PDBsum entry 2aw2
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Immune system
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PDB id
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2aw2
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References listed in PDB file
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Key reference
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Title
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Attenuating lymphocyte activity: the crystal structure of the btla-Hvem complex.
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Authors
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D.M.Compaan,
L.C.Gonzalez,
I.Tom,
K.M.Loyet,
D.Eaton,
S.G.Hymowitz.
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Ref.
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J Biol Chem, 2005,
280,
39553-39561.
[DOI no: ]
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PubMed id
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Abstract
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Five CD28-like proteins exert positive or negative effects on immune cells. Only
four of these five receptors interact with members of the B7 family. The
exception is BTLA (B and T lymphocyte attenuator), which instead interacts with
the tumor necrosis factor receptor superfamily member HVEM (herpes virus entry
mediator). To better understand this interaction, we determined the 2.8-A
crystal structure of the BTLA-HVEM complex. This structure shows that BTLA binds
the N-terminal cysteine-rich domain of HVEM and employs a unique binding surface
compared with other CD28-like receptors. Moreover, the structure shows that BTLA
recognizes the same surface on HVEM as gD (herpes virus glycoprotein D) and
utilizes a similar binding motif. Light scattering analysis demonstrates that
the extracellular domain of BTLA is monomeric and that BTLA and HVEM form a 1:1
complex. Alanine-scanning mutagenesis of HVEM was used to further define
critical binding residues. Finally, BTLA adopts an immunoglobulin I-set fold.
Despite structural similarities to other CD28-like members, BTLA represents a
unique co-receptor.
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Figure 1.
FIGURE 1. Complex of BTLA with HVEM. a, C-  rendering of BTLA
(yellow) and HVEM (CRD1, white; CRD2; light blue; CRD3, blue)
showing that BTLA binds the N-terminal cysteine-rich domain of
HVEM.  sheets are shown as
arrows. Cysteine residues are shows as sticks with the sulfur
atoms colored orange. b, C- rendering of BTLA with
strands labeled. C- atoms of predicted
N-glycosylation sites are shown as purple spheres. c, wall-eyed
stereo image of the BTLA-HVEM binding site showing the sheet
hydrogen bonding pattern formed at the interface. Residues of
interest are labeled. BTLA residues are underlined.
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Figure 4.
FIGURE 4. gD mimics BTLA. a, molecular surface of HVEM
(CDR1 white; CRD2, light blue; CRD3, blue) is shown with C- renderings of BTLA.
HVEM residues crucial for BTLA affinity (P17, V36, and Y23) are
colored red and labeled. b, molecular surface of HVEM colored as
in a with C- rendering of gD (N- and
C-terminal extensions, yellow; Ig domain, green). HVEM residues
crucial for gD affinity (C37 and Y23 (28)) are colored red and
labeled. c, sequence of the structurally similar short -strands
in BTLA and gD that bind HVEM.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2005,
280,
39553-39561)
copyright 2005.
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