1jtz
From Proteopedia
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'''CRYSTAL STRUCTURE OF TRANCE/RANKL CYTOKINE.''' | '''CRYSTAL STRUCTURE OF TRANCE/RANKL CYTOKINE.''' | ||
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[[Category: Fremont, D H.]] | [[Category: Fremont, D H.]] | ||
[[Category: Nelson, C A.]] | [[Category: Nelson, C A.]] | ||
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Revision as of 18:55, 2 May 2008
CRYSTAL STRUCTURE OF TRANCE/RANKL CYTOKINE.
Overview
RANK, the receptor activator of NF-kappaB, and its ligand RANKL (initially termed TRANCE, also termed ODF and OPGL), are a TNF superfamily receptor-ligand pair that govern the development and function of osteoclasts, lymphoid tissue, and mammary epithelium. While TNF family cytokines share a common structural scaffold, individual receptor-ligand pairs associate with high specificity. Given the low level of amino acid conservation among members of the TNF superfamily, the means by which these molecules achieve specificity cannot be completely understood without knowledge of their three-dimensional structures. To determine the elements of RANKL that mediate RANK activation, we have crystallized the ectodomain of murine RANKL and solved its structure to a resolution of 2.6 A. RANKL self-associates as a homotrimer with four unique surface loops that distinguish it from other TNF family cytokines. Mutagenesis of selected residues in these loops significantly modulates RANK activation, as evidenced by in vitro osteoclastogenesis, thereby establishing their necessity in mediating the biological activities of RANKL. Such structural determinants of RANKL-RANK specificity may be of relevance in the pharmacologic design of compounds to ameliorate osteopenic disorders of bone.
About this Structure
1JTZ is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity., Lam J, Nelson CA, Ross FP, Teitelbaum SL, Fremont DH, J Clin Invest. 2001 Oct;108(7):971-9. PMID:11581298 Page seeded by OCA on Fri May 2 21:55:08 2008
