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PDBsum entry 2h3n
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protein Protein-protein interface(s) links
Immune system PDB id
2h3n

 

 

 

 

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Contents
Protein chains
99 a.a. *
116 a.a. *
Waters ×68
* Residue conservation analysis
PDB id:
2h3n
Name: Immune system
Title: Crystal structure of a surrogate light chain (lambda5 and vpreb) homodimer
Structure: Vpreb protein. Chain: a, c. Synonym: immunoglobulin iota chain. V(pre)b protein. Cd179a antigen. Engineered: yes. Ig lambda-5. Chain: b, d. Synonym: immunoglobulin lambda-like polypeptide 1. Immunoglobulin- related protein 14.1. Immunoglobulin omega polypeptide. Cd179b antigen.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: vpreb1, vpreb. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_organ: eggs. Gene: igll1, igl1.
Resolution:
2.30Å     R-factor:   0.228     R-free:   0.281
Authors: A.J.Bankovich,K.C.Garcia
Key ref:
A.J.Bankovich et al. (2007). Structural insight into pre-B cell receptor function. Science, 316, 291-294. PubMed id: 17431183 DOI: 10.1126/science.1139412
Date:
22-May-06     Release date:   08-May-07    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P12018  (VPREB_HUMAN) -  Immunoglobulin iota chain from Homo sapiens
Seq:
Struc: 		145 a.a.
99 a.a.
Protein chains
Pfam   ArchSchema ?
P15814  (IGLL1_HUMAN) -  Immunoglobulin lambda-like polypeptide 1 from Homo sapiens
Seq:
Struc: 		213 a.a.
116 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1126/science.1139412 Science 316:291-294 (2007)
PubMed id: 17431183  
 
 
Structural insight into pre-B cell receptor function.
A.J.Bankovich, S.Raunser, Z.S.Juo, T.Walz, M.M.Davis, K.C.Garcia.
 
  ABSTRACT  
 
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.
 
  Selected figure(s)  
 
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. 		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.
 
  The above figures are reprinted by permission from the AAAs: Science (2007, 316, 291-294) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21354859 R.Berry, Z.Chen, J.McCluskey, and J.Rossjohn (2011).
Insight into the basis of autonomous immunoreceptor activation.
  Trends Immunol, 32, 165-170.  
21402931 S.J.Lin, Y.Hu, J.Zhu, T.K.Woodruff, and T.S.Jardetzky (2011).
Structure of betaglycan zona pellucida (ZP)-C domain provides insights into ZP-mediated protein polymerization and TGF-beta binding.
  Proc Natl Acad Sci U S A, 108, 5232-5236.
PDB code: 3qw9
20944732 B.Malissen, and H.Luche (2010).
Immunology: Egocentric pre-T-cell receptors.
  Nature, 467, 793-794.  
19822901 D.Corcos, M.J.Osborn, L.S.Matheson, F.Santos, X.Zou, J.A.Smith, G.Morgan, A.Hutchings, M.Hamon, D.Oxley, and M.Brüggemann (2010).
Immunoglobulin aggregation leading to Russell body formation is prevented by the antibody light chain.
  Blood, 115, 282-288.  
20622883 R.Ubelhart, M.P.Bach, C.Eschbach, T.Wossning, M.Reth, and H.Jumaa (2010).
N-linked glycosylation selectively regulates autonomous precursor BCR function.
  Nat Immunol, 11, 759-765.  
20145007 S.Minguet, E.P.Dopfer, and W.W.Schamel (2010).
Low-valency, but not monovalent, antigens trigger the B-cell antigen receptor (BCR).
  Int Immunol, 22, 205-212.  
19827951 T.Kurosaki, H.Shinohara, and Y.Baba (2010).
B cell signaling and fate decision.
  Annu Rev Immunol, 28, 21-55.  
19597006 A.J.Fried, and F.A.Bonilla (2009).
Pathogenesis, diagnosis, and management of primary antibody deficiencies and infections.
  Clin Microbiol Rev, 22, 396-414.  
19084434 F.Köhler, E.Hug, C.Eschbach, S.Meixlsperger, E.Hobeika, J.Kofer, H.Wardemann, and H.Jumaa (2008).
Autoreactive B cell receptors mimic autonomous pre-B cell receptor signaling and induce proliferation of early B cells.
  Immunity, 29, 912-921.  
18532877 J.L.Miller, J.Le Coq, A.Hodes, R.Barbalat, J.F.Miller, and P.Ghosh (2008).
Selective ligand recognition by a diversity-generating retroelement variable protein.
  PLoS Biol, 6, e131.
PDB code: 2iou
18287279 L.Morstadt, A.Bohm, D.Yüksel, K.Kumar, B.D.Stollar, and J.D.Baleja (2008).
Engineering and characterization of a single chain surrogate light chain variable domain.
  Protein Sci, 17, 458-465.
PDB code: 3bj9
18664586 L.Xu, H.Yee, C.Chan, A.K.Kashyap, L.Horowitz, M.Horowitz, R.R.Bhatt, and R.A.Lerner (2008).
Combinatorial surrobody libraries.
  Proc Natl Acad Sci U S A, 105, 10756-10761.  
18725575 T.W.LeBien, and T.F.Tedder (2008).
B lymphocytes: how they develop and function.
  Blood, 112, 1570-1580.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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