2QDN

Crystal Structure of mouse GITRL

Summary for 2QDN

• Entry DOI: 10.2210/pdb2qdn/pdb
• Descriptor: GITR ligand (2 entities in total)
• Functional Keywords: gitrl; glucocorticoid-induced tnf receptor ligand, immune system
• Biological source: Mus musculus (house mouse)
• Cellular location: Cell membrane ; Single-pass type II membrane protein : Q7TS55
• Total number of polymer chains: 2
• Total formula weight: 30022.81

Authors

Chattopadhyay, K.,Ramagopal, U.A.,Nathenson, S.G.,Almo, S.C. (deposition date: 2007-06-21, release date: 2008-01-01, Last modification date: 2017-10-18)

Primary citation

Chattopadhyay, K.,Ramagopal, U.A.,Brenowitz, M.,Nathenson, S.G.,Almo, S.C.
Evolution of GITRL immune function: murine GITRL exhibits unique structural and biochemical properties within the TNF superfamily.
Proc.Natl.Acad.Sci.Usa, 105:635-640, 2008

PubMed Abstract: Glucocorticoid-induced TNF receptor ligand (GITRL), a recently identified member of the TNF superfamily, binds to its receptor, GITR, on both effector and regulatory T cells and generates positive costimulatory signals implicated in a wide range of T cell functions. In contrast to all previously characterized homotrimeric TNF family members, the mouse GITRL crystal structure reveals a previously unrecognized dimeric assembly that is stabilized via a unique "domain-swapping" interaction. Consistent with its crystal structure, mouse GITRL exists as a stable dimer in solution. Structure-guided mutagenesis studies confirmed the determinants responsible for dimerization and support a previously unrecognized receptor-recognition surface for mouse GITRL that has not been observed for any other TNF family members. Taken together, the unique structural and biochemical behavior of mouse GITRL, along with the unusual domain organization of murine GITR, support a previously unrecognized mechanism for signaling within the TNF superfamily.

PubMed: 18182486
DOI: 10.1073/pnas.0710529105

Experimental method

X-RAY DIFFRACTION (2.09 Å)