PDBsum entry 2z63

Immune system

PDB id: 2z63

Contents

Protein chain

570 a.a. *

Ligands

NAG-NAG-FUL

NAG-NAG

Waters ×292

* Residue conservation analysis

PDB id:

2z63

Name:

Immune system

Title:

Crystal structure of the tv8 hybrid of human tlr4 and hagfish vlrb.61

Structure:

Toll-like receptor 4, variable lymphocyte receptor b. Chain: a. Fragment: tlr4, unp residues 27-527(human), vlrb.61, unp residues 133-199(inshore hagfish). Synonym: htoll, cd284 antigen, tv8. Engineered: yes

Source:

Homo sapiens, eptatretus burgeri. Human, inshore hagfish. Organism_taxid: 9606, 7764. Gene: tlr4, vlrb.61. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

2.00Å R-factor: 0.251 R-free: 0.298

Authors:

H.M.Kim,B.S.Park,J.-O.Lee

Key ref:

H.M.Kim et al. (2007). Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell, 130, 906-917. PubMed id: 17803912 DOI: 10.1016/j.cell.2007.08.002

Date:

22-Jul-07 Release date: 18-Sep-07

Protein chain

O00206  (TLR4_HUMAN) -  Toll-like receptor 4 from Homo sapiens

Seq: 839 a.a.

Struc: 570 a.a.*

Protein chain

Q4G1L2  (Q4G1L2_EPTBU) -  Variable lymphocyte receptor B from Eptatretus burgeri

Seq: 273 a.a.

Struc: 570 a.a.*

* PDB and UniProt seqs differ at 167 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.2.2.6 - ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase.
• Reaction: NAD⁺ + H2O = ADP-D-ribose + nicotinamide + H⁺

NAD(+) + H2O = ADP-D-ribose + nicotinamide + H(+) (Bound ligand (Het Group name = NAG) matches with 43.75% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/j.cell.2007.08.002

Cell 130:906-917 (2007)

PubMed id: 17803912

Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran.

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, J.O.Lee.

ABSTRACT

TLR4 and MD-2 form a heterodimer that recognizes LPS (lipopolysaccharide) from Gram-negative bacteria. Eritoran is an analog of LPS that antagonizes its activity by binding to the TLR4-MD-2 complex. We determined the structure of the full-length ectodomain of the mouse TLR4 and MD-2 complex. We also produced a series of hybrids of human TLR4 and hagfish VLR and determined their structures with and without bound MD-2 and Eritoran. TLR4 is an atypical member of the LRR family and is composed of N-terminal, central, and C-terminal domains. The beta sheet of the central domain shows unusually small radii and large twist angles. MD-2 binds to the concave surface of the N-terminal and central domains. The interaction with Eritoran is mediated by a hydrophobic internal pocket in MD-2. Based on structural analysis and mutagenesis experiments on MD-2 and TLR4, we propose a model of TLR4-MD-2 dimerization induced by LPS.

Selected figure(s)

Figure 1.
Figure 1. Overall Structure of the Mouse TLR4-MD-2 Complex
(A–C) Three views of the mouse TLR4-MD-2 complex are shown in the diagrams. The N-terminal, central, and C-terminal domains of TLR4 are colored in blue, cyan, and green, respectively. The beta strands of MD-2 are shown in pink and red, and the LRR modules of TLR4 are numbered.
(D) Closeup view of mouse MD-2. Disulfide bridges are shown in yellow and cysteines are labeled. Cys133 is not involved in the disulfide bridge formation. The orientation of this view is the same as for (C).

Figure 4.
Figure 4. Assembly of the Full-Length Ectodomain of Human TLR4
Structures of the three human TLR4-VLRB.61 hybrids. TLR4 fragments are colored blue and VLRB.61 fragments gray. The full-length ectodomain of human TLR4 was assembled after superimposition of the overlapping regions of the TV8 and VT3 hybrids. The disulfide bridges are represented in orange.

The above figures are reprinted by permission from Cell Press: Cell (2007, 130, 906-917) copyright 2007.

Figures were selected by an automated process.