PDBsum entry 3g3a

Hydrolase/immune system

PDB id: 3g3a

Contents

Protein chains

167 a.a. *

126 a.a. *

Waters ×578

* Residue conservation analysis

PDB id:

3g3a

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.

Resolution:

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

Date:

02-Feb-09 Release date: 23-Jun-09

Protein chains

D0VX18  (D0VX18_PETMA) -  Variable lymphocyte receptor VLRB.2D from Petromyzon marinus

Seq: 178 a.a.

Struc: 167 a.a.

Protein chains

P00698  (LYSC_CHICK) -  Lysozyme C from Gallus gallus

Seq: 147 a.a.

Struc: 126 a.a.

Enzyme reactions

• Enzyme class: Chains B, D, F, H: E.C.3.2.1.17 - lysozyme.
• 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.

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.

ABSTRACT

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.