Structural studies of the post-cleavage complex in V(D)J recombination

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications & trials

Abstract

Our research program aimed at understanding the functions of the RAG1-RAG2 protein complex in molecular detail has progressed in the past year. Our crystal structure of the proteins without DNA (2015) was a major advance, but left questions about mechanism unanswered. Although we were able to give an explanation of the so called 12/23 rule in V(D)J recombination by modeling appropriate DNA fragments into the structure, it was essential to obtain detailed information on structures containing DNA at all stages of the cleavage reaction. Crystals of several of these species have now been obtained and are in the process of being further refined. Our work on RAG mutations that are known to cause severe combined immune deficiency (SCID), or a variant form of the same disorder known as Omenn syndrome is also continuing, with further analysis of specific mutated residues.