3B2D

Crystal structure of human RP105/MD-1 complex

Summary for 3B2D

• Entry DOI: 10.2210/pdb3b2d/pdb
• Descriptor: CD180 antigen, Lymphocyte antigen 86, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: protein-protein complex, leucine rich repeat md-2 related lipid recognition, receptor innate immunity, glycosylation, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: Q99467; Secreted, extracellular space: O95711
• Total number of polymer chains: 4
• Total formula weight: 171036.23

Authors

Ohto, U.,Shimizu, T. (deposition date: 2011-07-29, release date: 2011-11-09, Last modification date: 2024-11-20)

Primary citation

Ohto, U.,Miyake, K.,Shimizu, T.
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, 2011

PubMed 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.

PubMed: 21959264
DOI: 10.1016/j.jmb.2011.09.020

Experimental method

X-RAY DIFFRACTION (2.8 Å)