PDBsum entry 3g3a

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protein Protein-protein interface(s) links
Hydrolase/immune system PDB id
Protein chains
167 a.a. *
126 a.a. *
Waters ×578
* Residue conservation analysis
PDB id:
Name: Hydrolase/immune system
Title: Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen
Structure: Variable lymphocyte receptor vlrb.2d. Chain: a, c, e, g. Fragment: ectodomain. Engineered: yes. LysozymE C. Chain: b, d, f, h. Synonym: 1,4-beta-n-acetylmuramidasE C, allergen gal d iv. Engineered: yes
Source: Petromyzon marinus. Sea lamprey. Organism_taxid: 7757. Gene: vlr. Expressed in: escherichia coli. Expression_system_taxid: 562. Gallus gallus. Bantam,chickens. Organism_taxid: 9031.
2.20Å     R-factor:   0.222     R-free:   0.271
Authors: L.Deng,C.A.Velikovsky,R.A.Mariuzza
Key ref:
C.A.Velikovsky et al. (2009). Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen. Nat Struct Biol, 16, 725-730. PubMed id: 19543291 DOI: 10.1038/nsmb.1619
02-Feb-09     Release date:   23-Jun-09    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
D0VX18  (D0VX18_PETMA) -  Variable lymphocyte receptor VLRB.2D
178 a.a.
167 a.a.
Protein chains
Pfam   ArchSchema ?
P00698  (LYSC_CHICK) -  Lysozyme C
147 a.a.
126 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains B, D, F, H: E.C.  - Lysozyme.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     6 terms  


DOI no: 10.1038/nsmb.1619 Nat Struct Biol 16:725-730 (2009)
PubMed id: 19543291  
Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen.
C.A.Velikovsky, L.Deng, S.Tasumi, L.M.Iyer, M.C.Kerzic, L.Aravind, Z.Pancer, R.A.Mariuzza.
Variable lymphocyte receptors (VLRs) are leucine-rich repeat proteins that mediate adaptive immunity in jawless vertebrates. VLRs are fundamentally different from the antibodies of jawed vertebrates, which consist of immunoglobulin (Ig) domains. We determined the structure of an anti-hen egg white lysozyme (HEL) VLR, isolated by yeast display, bound to HEL. The VLR, whose affinity resembles that of IgM antibodies, uses nearly all its concave surface to bind the protein, in addition to a loop that penetrates into the enzyme active site. The VLR-HEL structure combined with sequence analysis revealed an almost perfect match between ligand-contacting positions and positions with highest sequence diversity. Thus, it is likely that we have defined the generalized antigen-binding site of VLRs. We further demonstrated that VLRs can be affinity-matured by 13-fold to affinities as high as those of IgG antibodies, making VLRs potential alternatives to antibodies for biotechnology applications.
  Selected figure(s)  
Figure 1.
(a) Ribbon diagram of the VLRB.2D–HEL complex showing the concave antigen-binding surface of the VLR solenoid. LRRNT, yellow; LRR1, LRRV1 and LRRVe, blue; CP, red; LRRCT, orange; HEL, green; residue numbers corresponding to each module in parentheses. (b) The complex is oriented to highlight the interaction between the LRRCT insert and the active site cleft of HEL.
Figure 3.
Residues involved in contacts are depicted as surface representation. (a) Binding surface of VLRB.2D with contacting residues from LRR1, LRRV and LRRVe in blue, from CP in red and from LRRCT in orange. (b) Binding surface of VLR RBC36 (cyan) in the complex with H-saccharide based on the structure PDB 3E6J^4. (c,d) Comparison of VLR and antibody epitopes on HEL. Binding surfaces of HEL in the VLRB.2D–HEL complex (c) and camel cAb-Lys3–HEL based on the complex structure PDB 1MEL^14 (d). Residues forming contacts in both complexes are green; residues that interact exclusively with VLRB.2D or cAb-Ly3 are violet.
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: Nat Struct Biol (2009, 16, 725-730) copyright 2009.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21227671 E.Hsu (2011).
The invention of lymphocytes.
  Curr Opin Immunol, 23, 156-162.  
21481769 I.Botos, D.M.Segal, and D.R.Davies (2011).
The structural biology of Toll-like receptors.
  Structure, 19, 447-459.  
20651744 G.W.Litman, J.P.Rast, and S.D.Fugmann (2010).
The origins of vertebrate adaptive immunity.
  Nat Rev Immunol, 10, 543-553.  
20660745 J.Kasamatsu, Y.Sutoh, K.Fugo, N.Otsuka, K.Iwabuchi, and M.Kasahara (2010).
Identification of a third variable lymphocyte receptor in the lamprey.
  Proc Natl Acad Sci U S A, 107, 14304-14308.  
20616002 L.Deng, C.A.Velikovsky, G.Xu, L.M.Iyer, S.Tasumi, M.C.Kerzic, M.F.Flajnik, L.Aravind, Z.Pancer, and R.A.Mariuzza (2010).
A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey.
  Proc Natl Acad Sci U S A, 107, 13408-13413.
PDB codes: 3m18 3m19
19997068 M.F.Flajnik, and M.Kasahara (2010).
Origin and evolution of the adaptive immune system: genetic events and selective pressures.
  Nat Rev Genet, 11, 47-59.  
20075989 N.Kishishita, T.Matsuno, Y.Takahashi, H.Takaba, H.Nishizumi, and F.Nagawa (2010).
Regulation of antigen-receptor gene assembly in hagfish.
  EMBO Rep, 11, 126-132.  
20056434 N.R.Saha, J.Smith, and C.T.Amemiya (2010).
Evolution of adaptive immune recognition in jawless vertebrates.
  Semin Immunol, 22, 25-33.  
20482318 R.A.Mariuzza, C.A.Velikovsky, L.Deng, G.Xu, and Z.Pancer (2010).
Structural insights into the evolution of the adaptive immune system: the variable lymphocyte receptors of jawless vertebrates.
  Biol Chem, 391, 753-760.  
20804457 S.Brunner, S.Hurni, P.Streckeisen, G.Mayr, M.Albrecht, N.Yahiaoui, and B.Keller (2010).
Intragenic allele pyramiding combines different specificities of wheat Pm3 resistance alleles.
  Plant J, 64, 433-445.  
19625627 S.Tasumi, C.A.Velikovsky, G.Xu, S.A.Gai, K.D.Wittrup, M.F.Flajnik, R.A.Mariuzza, and Z.Pancer (2009).
High-affinity lamprey VLRA and VLRB monoclonal antibodies.
  Proc Natl Acad Sci U S A, 106, 12891-12896.  
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 codes are shown on the right.