Sam domains in multiple diseases.

BACKGROUND: The sterile alpha motif (Sam) domain is a small helical protein module able to undergo homo- and hetero-oligomerization as well as polymerization thus forming different types of protein architectures. A few Sam domains are involved in pathological processes and consequently, they represent valuable targets for the development of new potential therapeutic routes. This study intends to collect state-of-the-art knowledge on the different modes by which Sam domains can favor disease onset and progression.

METHODS: This review was build up by looking throughout the literature for: a) the structural properties of Sam domains, b) interactions mediated by a Sam module, c) presence of a Sam domain in proteins relevant for a specific disease.

RESULTS: Sam domains appear crucial in many diseases including but not limited to cataracts, cancer, renal disorders. Often pathologies are linked to mutations directly positioned in the Sam domains that alter its stability and/or affect interactions that are crucial for proper protein functions. In only a few diseases the Sam motif plays a kind of "side role" and cooperates to the pathological event by enhancing the action of a different protein domain.

CONCLUSION: Considering the many roles of the Sam domain into a significant variety of diseases, more efforts and novel drug discovery campaigns need to be engaged to find out small molecules and/or peptides targeting Sam domains. Such compounds may represent the pillars on which to build novel therapeutic strategies to cure different pathologies.