Sam Domains in Multiple Diseases.

Abstract:

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 searching 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 cancer, renal disorders, cataracts. Often pathologies are linked to mutations directly positioned in the Sam domains that alter their 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.

journal_name

Curr Med Chem

authors

Vincenzi M,Mercurio FA,Leone M

doi

10.2174/0929867325666181009114445

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

450-476

issue

3

eissn

0929-8673

issn

1875-533X

pii

CMC-EPUB-93541

journal_volume

27

pub_type

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