PDBsum entry 3t6q

Immune system

PDB id: 3t6q

Contents

Protein chains

601 a.a.

139 a.a.

Ligands

NAG-NAG-BMA-MAN-MAN-MAN-MAN-MAN-MAN

NAG-NAG ×3

NAG-NAG-BMA-MAN-MAN-MAN-MAN-MAN

GOL ×15

NAG ×13

Metals

_CU

Waters ×1149

PDB id:

3t6q

Name:

Immune system

Title:

Crystal structure of mouse rp105/md-1 complex

Structure:

Cd180 antigen. Chain: a, b. Fragment: unp residues 21-626. Synonym: lymphocyte antigen 78, ly-78, radioprotective 105 kda protein. Engineered: yes. Lymphocyte antigen 86. Chain: c, d. Synonym: ly-86, protein md-1.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: cd180, ly78, rp105. Expressed in: drosophila. Expression_system_taxid: 7215. Expression_system_cell: s2. Gene: ly86, md1. Expression_system_cell: s2

Resolution:

1.90Å R-factor: 0.188 R-free: 0.231

Authors:

U.Ohto,T.Shimizu

Key ref:

U.Ohto et al. (2011). Crystal structures of mouse and human RP105/MD-1 complexes reveal unique dimer organization of the toll-like receptor family. J Mol Biol, 413, 815-825. PubMed id: 21959264

Date:

28-Jul-11 Release date: 09-Nov-11

Protein chains

Q62192  (CD180_MOUSE) -  CD180 antigen from Mus musculus

Seq: 661 a.a.

Struc: 601 a.a.*

Protein chains

O88188  (LY86_MOUSE) -  Lymphocyte antigen 86 from Mus musculus

Seq: 162 a.a.

Struc: 139 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

J Mol Biol 413:815-825 (2011)

PubMed id: 21959264

Crystal structures of mouse and human RP105/MD-1 complexes reveal unique dimer organization of the toll-like receptor family.

U.Ohto, K.Miyake, T.Shimizu.

ABSTRACT

The Toll-like receptor (TLR) 4/MD-2 heterodimer senses lipopolysaccharide (LPS). RP105 (radioprotective 105 kDa), a TLR-related molecule, is similar to TLR4 in that the extracellular leucine-rich repeats associate with MD-1, the MD-2-like molecule. MD-2 has a unique hydrophobic cavity that directly binds to lipid A, the active center of LPS. LPS-bound MD-2 opens the secondary interface with TLR4, leading to dimerization of TLR4/MD-2. MD-1 also has a hydrophobic cavity that accommodates lipid IVa, a precursor of lipid A, suggesting a role for the RP105/MD-1 heterodimer in sensing LPS or related microbial products. Little is known, however, about the structure of the RP105/MD-1 heterodimer or its oligomer. Here, we have determined the crystal structures of mouse and human RP105/MD-1 complexes at 1.9 and 2.8 Å resolutions, respectively. Both mouse and human RP105/MD-1 exhibit dimerization of the 1:1 RP105/MD-1 complex, demonstrating a novel organization. The "m"-shaped 2:2 RP105/MD-1 complex exhibits an inverse arrangement, with N-termini interacting in the middle. Thus, the dimerization interface of RP105/MD-1 is located on the opposite side of the complex, compared to the 2:2 TLR4/MD-2 complex. These results demonstrate that the 2:2 RP105/MD-1 complex is distinct from previously reported TLR dimers, including TLR4/MD-2, TLR1/TLR2, TLR2/TLR6, and TLR3, all of which facilitate homotypic or heterotypic interaction of the C-terminal cytoplasmic signaling domain.