View source for 1i85

[[Image:1i85.jpg|left|200px]]<br /><applet load="1i85" size="350" color="white" frame="true" align="right" spinBox="true" 
caption="1i85, resolution 3.2&Aring;" />
'''CRYSTAL STRUCTURE OF THE CTLA-4/B7-2 COMPLEX'''<br />

==Overview==
Regulation of T-cell activity is dependent on antigen-independent, co-stimulatory signals provided by the disulphide-linked homodimeric, T-cell surface receptors, CD28 and CTLA-4 (ref. 1). Engagement of CD28, with B7-1 and B7-2 ligands on antigen-presenting cells (APCs) provides a, stimulatory signal for T-cell activation, whereas subsequent engagement of, CTLA-4 with these same ligands results in attenuation of the response., Given their central function in immune modulation, CTLA-4- and, CD28-associated signalling pathways are primary therapeutic targets for, preventing autoimmune disease, graft versus host disease, graft rejection, and promoting tumour immunity. However, little is known about the, cell-surface organization of these receptor/ligand complexes and the, structural basis for signal transduction. Here we report the 3.2-A, resolution structure of the complex between the disulphide-linked, homodimer of human CTLA-4 and the receptor-binding domain of human B7-2., The unusual dimerization properties of both CTLA-4 and B7-2 place their, respective ligand-binding sites distal to the dimer interface in each, molecule and promote the formation of an alternating arrangement of, bivalent CTLA-4 and B7-2 dimers that extends throughout the crystal., Direct observation of this CTLA-4/B7-2 network provides a model for the, periodic organization of these molecules within the immunological synapse, and suggests a distinct mechanism for signalling by dimeric cell-surface, receptors.

==Disease==
Known diseases associated with this structure: Celiac disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=123890 123890]], Diabetes mellitus, insulin-dependent, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=123890 123890]], Graves disease, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=123890 123890]], Hypothyroidism, autoimmune OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=123890 123890]]

==About this Structure==
1I85 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1I85 OCA]. 

==Reference==
Structural basis for co-stimulation by the human CTLA-4/B7-2 complex., Schwartz JC, Zhang X, Fedorov AA, Nathenson SG, Almo SC, Nature. 2001 Mar 29;410(6828):604-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11279501 11279501]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Almo, S.C.]]
[[Category: Fedorov, A.A.]]
[[Category: Nathenson, S.G.]]
[[Category: Schwartz, J.C.D.]]
[[Category: Zhang, X.]]
[[Category: ig v-type domain]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:59:56 2008''