InterPro domain: IPR001660

The sterile alpha motif (SAM) domain is a putative protein interaction module present in a wide variety of proteins [ 1 ] involved in many biological processes. The SAM domain that spreads over around 70 residues is found in diverse eukaryotic organisms [ 2 ]. SAM domains have been shown to homo- and hetero-oligomerise, forming multiple self-association architectures and also binding to various non-SAM domain-containing proteins [ 3 ], nevertheless with a low affinity constant [ 4 ]. SAM domains also appear to possess the ability to bind RNA [ 5 ]. Smaug, a protein that helps to establish a morphogen gradient in Drosophila embryos by repressing the translation of nanos (nos) mRNA, binds to the 3' untranslated region (UTR) of nos mRNA via two similar hairpin structures. The 3D crystal structure of the Smaug RNA-binding region shows a cluster of positively charged residues on the Smaug-SAM domain, which could be the RNA-binding surface. This electropositive potential is unique among all previously determined SAM-domain structures and is conserved among Smaug-SAM homologues. These results suggest that the SAM domain might have a primary role in RNA binding.

Structural analyses show that the SAM domain is arranged in a small five-helix bundle with two large interfaces [ 6 ]. In the case of the SAM domain of EphB2, each of these interfaces is able to form dimers. The presence of these two distinct intermonomers binding surface suggest that SAM could form extended polymeric structures [ 6 ].

1. SAM as a protein interaction domain involved in developmental regulation. Protein Sci. 6, 249-53
2. The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization. Nat. Struct. Biol. 6, 44-9
3. A domain shared by the Polycomb group proteins Scm and ph mediates heterotypic and homotypic interactions. Mol. Cell. Biol. 17, 6683-92
4. Oligomeric structure of the human EphB2 receptor SAM domain. Science 283, 833-6
5. SAM domains: uniform structure, diversity of function. Trends Biochem. Sci. 28, 625-8