Title : The crystal structure of the costimulatory
OX40-
OX40L complex
Abstract :
- OX40 is a T cell costimulator activated by OX40L
- Blockade of the OX40L- OX40 interaction has ameliorative effects in animal models of T cell pathologies
- In order to better understand the interaction between OX40 and OX40L , we have determined the crystal structure of murine OX40L and of the human OX40- OX40L complex at 1.45 and 2.4 A, respectively
- These structures show that OX40L is an unusually small member of the tumor necrosis factor superfamily (TNFSF)
- The arrangement of the OX40L protomers forming the functional trimer is atypical and differs from that of other members by a 15 degrees rotation of each protomer with respect to the trimer axis, resulting in an open assembly
- Site-directed changes of the interfacial residues of OX40L suggest this interface lacks a single "hot spot" and that instead, binding energy is dispersed over at least two distinct areas
- These structures demonstrate the structural plasticity of TNFSF members and their interactions with receptors
Output (sent_index, trigger,
protein,
sugar,
site):
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):