NMR Studies of a Heterotypic SAM-SAM Association: The Interaction between SHIP2-SAM and ARAP3-SAM

Sterile alpha motif (Sam) domains are small protein modules that can be involved in homotypic or heterotypic associations and play several functions. Previous studies have reported that the Sam domain of the lipid phosphatase Ship2 can hetero-dimerize with the Sam domain of the PI3K effector protein Arap3. Here, we report on the NMR solution structure of Arap3-Sam and binding studies with Ship2-Sam. This work reveals that Arap3-Sam may associate with Ship2-Sam by adopting a known binding mode for Sam domains. Our studies further clarify the structural features that are important for Sam-Sam associations and give additional insights for the identification of small-molecule inhibitors of these interactions.