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PDBsum entry 2h3n
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Immune system
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PDB id
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2h3n
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References listed in PDB file
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Key reference
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Title
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Structural insight into pre-B cell receptor function.
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Authors
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A.J.Bankovich,
S.Raunser,
Z.S.Juo,
T.Walz,
M.M.Davis,
K.C.Garcia.
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Ref.
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Science, 2007,
316,
291-294.
[DOI no: ]
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PubMed id
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Abstract
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The pre-B cell receptor (pre-BCR) serves as a checkpoint in B cell development.
In the 2.7 angstrom structure of a human pre-BCR Fab-like fragment, consisting
of an antibody heavy chain (HC) paired with the surrogate light chain, the
"unique regions" of VpreB and lambda5 replace the
complementarity-determining region 3 (CDR3) loop of an antibody light chain and
appear to "probe" the HC CDR3, potentially influencing the selection
of the antibody repertoire. Biochemical analysis indicates that the pre-BCR is
impaired in its ability to recognize antigen, which, together with electron
microscopic visualization of a pre-BCR dimer, suggests ligand-independent
oligomerization as the likely signaling mechanism.
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Figure 1.
Fig. 1. Overall structure of the pre-BCR. (A) Cartoon
representation of the pre-BCR complex with the Fab-like arm of
the pre-BCR that was crystallized (dashed box). (B) Ribbon
representation of the pre-BCR structure [dashed box in (A)].
Three protein chains are included in the model: VpreB (yellow),
 5 (magenta), and
HC (blue). Missing portions of the molecule are indicated with
residue numbers and dashed lines at the N terminus of 5
and the C terminus of VpreB. (C) Schematic representation of the
V-type Ig fold formed by VpreB and 5. ß
strands are designated by arrows labeled a to g. VpreB loops
that are homologous to Fab CDRs are labeled. The dashed
rectangle indicates the portion of the structure shown in (D).
The red line with "SS" indicates the intracellular domain
disulfide bond. (D) 2.7 Å electron density map (  [A]-weighted
2F[o] – F[c], where F[o] and F[c] are the observed and
calculated structure factors; contoured to 1.2 )
showing the a and f strands of VpreB and the g strand of 5.
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Figure 2.
Fig. 2. The pre-BCR CDR3-H sensing site. (A) Surface
representation of the pre-BCR structure in the same orientation
as shown in Fig. 1B. The VpreB unique region exits out the top
of the domain, lying over the HC antigen-combining site. (B)
Contact residues (29) within the SLC/HC interface zoomed into
the region demarcated by the red dashed box in (A). The main
chain is depicted as ribbons with contact residue side chains as
sticks. SLC, red; HC, blue. Asterisk designates the interchain
salt bridge between VpreB and HC. (C) At left, the CDR3-H (blue
sticks) from the HC on the surface of the VpreB/ 5
segment of the SLC, showing the extent of interactions between
CDR3-H and the VpreB/ 5. The contact
footprint between CDR3-H and SLC is highlighted in red. To the
right, a similar projection of the CDR3-H on the surface of the
LC of a Fab. The contact footprint between CDR3-H and LC is
highlighted in red. The CDR3-H sequence is added below both
structures with the region shown in sticks highlighted (blue
letters). (D) Residues demarcating the human pre-BCR CDR3-H
sensing site. CDR3-H with side chains (blue), 5
(magenta), and VpreB (yellow) are shown. Pre-BCR side chains
that vary between human and mice and contact CDR3-H are shown in
cyan. The dashed line indicates a hydrogen bond. Below the
structure, a table of amino acid differences between mice and
humans in the region of the CDR3-H sensing site is appended.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2007,
316,
291-294)
copyright 2007.
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