Poster Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

Structural studies of the complex between the autoantigen GAD65 and the human mAb B96.11 (#123)

Liah Clark 1 , James S Green 1 , Benjamin T Porebski 1 , Nicholas J McKenzie 1 , Blake T Riley 1 , Itamar Kass 1 , David E Hoke 1 , Ashley M Buckle 1
  1. Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia

The human neuroendocrine enzyme glutamate decarboxylase (GAD) catalyses the synthesis of the inhibitory neurotransmitter GABA, using pyridoxal-5’-phosphate as cofactor. GAD exists as two isoforms named according to their respective molecular weights, GAD65 and GAD67. GAD65, but not GAD67, is a prevalent autoantigen, with autoantibodies to GAD65 being detected at high frequency in patients with autoimmune (type 1) diabetes and certain other autoimmune disorders. Using Small Angle X-ray Scattering and mutagenesis we describe an investigation into the structure of a complex between GAD65 and a recombinant Fab fragment derived from the human monoclonal antibody b96.11.