Dr. David Isenman portrait

Dr. David Isenman

In a study published in the April 29th issue of Science, Professor David Isenman of Biochemistry and Jean van den Elsen of the University of Bath shed light on the complex between complement receptor 2 and its ligand C3d, both of which are constituents of an innate immune system of our body known as complement.

The molecular details of the CR2-C3d interface have been mired in controversy for the past decade. Specifically, in 2001 an X-ray crystal structure of the complex consisting of C3d and the first two domains of CR2 was published in Science. However, from the start, that structure was discordant with much biochemical data in the literature, and over the years the discrepancies have only increased.

“We recognize that the goal of applying this knowledge to autoimmune therapies and enhanced vaccine efficiency will not be trivial. But the structural scaffold for further discoveries is now in place,” said Isenman.

The detailed knowledge of the receptor-ligand interface provided by the new structure of this complex has implications as both a potential therapeutic target, in the case of antibody-mediated autoimmune diseases, and as something that may be exploited in enhancing the efficacy of vaccines.