PDBsum entry 2o6q

Immune system

PDB id

2o6q

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Contents

			Protein chain

					270 a.a. *

			Waters ×215

* Residue conservation analysis

PDB id:

2o6q

Links

Name:

Immune system

Title:

Structural diversity of the hagfish variable lymphocyte receptors a29

Structure:

Variable lymphocyte receptor a. Chain: a. Fragment: leucine-rich repeat (lrr), residues 23-292. Synonym: variable lymphocyte receptor a29. Engineered: yes

Source:

Eptatretus burgeri. Inshore hagfish. Organism_taxid: 7764. Gene: vlra. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: hi5.

Resolution:

2.50Å

R-factor:

0.227

R-free:

0.264

Authors:

J.O.Lee,H.M.Kim,S.C.Oh

Key ref:

H.M.Kim et al. (2007). Structural diversity of the hagfish variable lymphocyte receptors. J Biol Chem, 282, 6726-6732. PubMed id: 17192264 DOI: 10.1074/jbc.M608471200

Date:

08-Dec-06

Release date:

26-Dec-06

PROCHECK

	Headers

	References

Protein chain

Q32R26 (Q32R26_EPTBU) - Variable lymphocyte receptor A from Eptatretus burgeri

Seq: Struc:					371 a.a. 270 a.a.

Key:

PfamA domain

Secondary structure

CATH domain

DOI no: 10.1074/jbc.M608471200	J Biol Chem 282:6726-6732 (2007)
PubMed id: 17192264

Structural diversity of the hagfish variable lymphocyte receptors.
H.M.Kim, S.C.Oh, K.J.Lim, J.Kasamatsu, J.Y.Heo, B.S.Park, H.Lee, O.J.Yoo, M.Kasahara, J.O.Lee.

ABSTRACT

Variable lymphocyte receptors (VLRs) are recently discovered leucine-rich repeat (LRR) family proteins that mediate adaptive immune responses in jawless fish. Phylogenetically it is the oldest adaptive immune receptor and the first one with a non-immunoglobulin fold. We present the crystal structures of one VLR-A and two VLR-B clones from the inshore hagfish. The hagfish VLRs have the characteristic horseshoe-shaped structure of LRR family proteins. The backbone structures of their LRR modules are highly homologous, and the sequence variation is concentrated on the concave surface of the protein. The conservation of key residues suggests that our structures are likely to represent the LRR structures of the entire repertoire of jawless fish VLRs. The analysis of sequence variability, prediction of protein interaction surfaces, amino acid composition analysis, and structural comparison with other LRR proteins suggest that the hypervariable concave surface is the most probable antigen binding site of the VLR.

Selected figure(s)



	Figure 2. FIGURE 2. Crystal structure of hagfish VLR-A. A, stereo view of Eb7VLRA.29. Blue, LRRNT; green, LRR modules; orange, LRRCT; gray, disulfide bridge; magenta, phenylalanine spine and asparagine ladder. B, top view of Eb7VLRA.29. This figure was generated using PyMOL.		Figure 3. FIGURE 3. Crystal structure of hagfish VLR-B and structure alignment of VLR-A and VLR-B. A, stereo view of Eb8VLRB.61. Blue, LRRNT; green, LRR modules; orange, LRRCT; gray, disulfide bridge; magenta, phenylalanine spine and asparagine ladder. B, alignment of the N-terminal half of Eb8VLRB.61 with that of Eb7VLRA.29. The r.m.s. deviation of the C positions is 0.55 Å. C, alignment of the C-terminal half of Eb8VLRB.61 with that of Eb7VLRA.29. The r.m.s. deviation of the C positions is 0.84 Å.

Figures were selected by the author.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21475308

T.Boehm (2011).
Design principles of adaptive immune systems.

Nat Rev Immunol, 11, 307-317.

20195622

J.J.Smith, A.B.Stuart, T.Sauka-Spengler, S.W.Clifton, and C.T.Amemiya (2010).
Development and analysis of a germline BAC resource for the sea lamprey, a vertebrate that undergoes substantial chromatin diminution.

Chromosoma, 119, 381-389.

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.

20613726

J.Yan, and R.W.Aldrich (2010).
LRRC26 auxiliary protein allows BK channel activation at resting voltage without calcium.

Nature, 466, 513-516.

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.

19543291

C.A.Velikovsky, L.Deng, S.Tasumi, L.M.Iyer, M.C.Kerzic, L.Aravind, Z.Pancer, and R.A.Mariuzza (2009).
Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen.

Nat Struct Mol Biol, 16, 725-730.

PDB codes:

3g39 3g3a 3g3b

19595807

I.Botos, L.Liu, Y.Wang, D.M.Segal, and D.R.Davies (2009).
The toll-like receptor 3:dsRNA signaling complex.

Biochim Biophys Acta, 1789, 667-674.

19931471

J.Y.Kang, X.Nan, M.S.Jin, S.J.Youn, Y.H.Ryu, S.Mah, S.H.Han, H.Lee, S.G.Paik, and J.O.Lee (2009).
Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer.

Immunity, 31, 873-884.

PDB codes:

3a79 3a7b 3a7c

19816595

K.Jung, J.E.Lee, H.Z.Kim, H.M.Kim, B.S.Park, S.I.Hwang, J.O.Lee, S.C.Kim, and G.Y.Koh (2009).
Toll-like receptor 4 decoy, TOY, attenuates gram-negative bacterial sepsis.

PLoS One, 4, e7403.

19452560

K.L.Hindle, J.Bella, and S.C.Lovell (2009).
Quantitative analysis and prediction of curvature in leucine-rich repeat proteins.

Proteins, 77, 342-358.

19627256

S.Carpenter, and L.A.O'Neill (2009).
Recent insights into the structure of Toll-like receptors and post-translational modifications of their associated signalling proteins.

Biochem J, 422, 1.

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.

19818630

T.P.Monie, C.E.Bryant, and N.J.Gay (2009).
Activating immunity: lessons from the TLRs and NLRs.

Trends Biochem Sci, 34, 553-561.

18238899

B.R.Herrin, M.N.Alder, K.H.Roux, C.Sina, G.R.Ehrhardt, J.A.Boydston, C.L.Turnbough, and M.D.Cooper (2008).
Structure and specificity of lamprey monoclonal antibodies.

Proc Natl Acad Sci U S A, 105, 2040-2045.

18818359

B.W.Han, B.R.Herrin, M.D.Cooper, and I.A.Wilson (2008).
Antigen recognition by variable lymphocyte receptors.

Science, 321, 1834-1837.

PDB code:

3e6j

19267632

M.Kasahara, J.Kasamatsu, and Y.Sutoh (2008).
Two types of antigen receptor systems in vertebrates.

Zoolog Sci, 25, 969-975.

18246071

M.N.Alder, B.R.Herrin, A.Sadlonova, C.R.Stockard, W.E.Grizzle, L.A.Gartland, G.L.Gartland, J.A.Boydston, C.L.Turnbough, and M.D.Cooper (2008).
Antibody responses of variable lymphocyte receptors in the lamprey.

Nat Immunol, 9, 319-327.

18701082

M.S.Jin, and J.O.Lee (2008).
Structures of the toll-like receptor family and its ligand complexes.

Immunity, 29, 182-191.

18156467

N.Courtemanche, and D.Barrick (2008).
Folding thermodynamics and kinetics of the leucine-rich repeat domain of the virulence factor Internalin B.

Protein Sci, 17, 43-53.

18462675

N.Courtemanche, and D.Barrick (2008).
The leucine-rich repeat domain of Internalin B folds along a polarized N-terminal pathway.

Structure, 16, 705-714.

18392023

Z.Pancer, and R.A.Mariuzza (2008).
The oldest antibodies newly discovered.

Nat Biotechnol, 26, 402-403.

17703932

G.W.Litman, L.J.Dishaw, J.P.Cannon, R.N.Haire, and J.P.Rast (2007).
Alternative mechanisms of immune receptor diversity.

Curr Opin Immunol, 19, 526-534.

17803912

H.M.Kim, B.S.Park, J.I.Kim, S.E.Kim, J.Lee, S.C.Oh, P.Enkhbayar, N.Matsushima, H.Lee, O.J.Yoo, and J.O.Lee (2007).
Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran.

Cell, 130, 906-917.

PDB codes:

2z62 2z63 2z64 2z65 2z66

17468760

I.B.Rogozin, L.M.Iyer, L.Liang, G.V.Glazko, V.G.Liston, Y.I.Pavlov, L.Aravind, and Z.Pancer (2007).
Evolution and diversification of lamprey antigen receptors: evidence for involvement of an AID-APOBEC family cytosine deaminase.

Nat Immunol, 8, 647-656.

17889651

M.S.Jin, S.E.Kim, J.Y.Heo, M.E.Lee, H.M.Kim, S.G.Paik, H.Lee, and J.O.Lee (2007).
Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide.

Cell, 130, 1071-1082.

PDB codes:

2z7x 2z80 2z81 2z82

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.