Crystal structure of the receptor-binding domain of human B7-2: Insights into organization and signaling
AUTOR(ES)
Zhang, Xuewu
FONTE
The National Academy of Sciences
RESUMO
B7-1 and B7-2 are homologous costimulatory ligands expressed on the surfaces of antigen-presenting cells. Their interactions with CD28/CTLA-4 receptors expressed on T cell surfaces are crucial for the proper regulation of T cell activity. B7-1 and B7-2 display distinct roles in immune regulation, although they are usually considered to have redundant functions. Here, we report the crystal structure of the receptor-binding (Ig V-type) domain of human B7-2 at 2.7-Å resolution. Structures of unliganded and liganded B7-1 and B7-2 suggest a physical–chemical basis for the observed functional similarities and differences between these two costimulatory ligands. Of particular note, whereas the majority of the residues mediating B7-1 dimerization are hydrophobic, the B7-2 dimer observed in the B7-2/CTLA-4 complex displays a very hydrophilic dimer interface. These differences provide a mechanism for preventing the formation of B7-1/B7-2 heterodimers. The divergence at the putative dimer interface is also consistent with the lower tendency of B7-2 to dimerize, as shown by the monomeric state of unliganded B7-2 both in solution and crystalline form, and may result in detailed differences in signaling mechanisms associated with B7-1 and B7-2.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=151384Documentos Relacionados
- Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor
- Structure of the receptor-binding domain of human thrombopoietin determined by complexation with a neutralizing antibody fragment
- Receptor-binding domain of murine leukemia virus envelope glycoproteins.
- Receptor-Binding Properties of a Soluble Form of Human Cytomegalovirus Glycoprotein B
- Identification of a Receptor-Binding Domain of Bordetella Dermonecrotic Toxin