The NMR structure of the murine DLC2 SAM domain reveals a variant fold that is similar to a four-helix bundle

Department of Biology, York University, Toronto, Ontario, Canada. <>
BMC Structural Biology (Impact Factor: 1.18). 02/2007; 7(1):34. DOI: 10.1186/1472-6807-7-34
Source: PubMed


The tumor suppressor DLC2 (Deleted in Liver Cancer -2) participates in cell signaling at the mitochondrial membrane. DLC2 is characterized by a SAM (sterile alpha motif) domain, a Rho GTPase activating protein (GAP) domain, and a START lipid transfer domain.
Towards understanding the function of DLC2, we have solved the NMR solution structure of the SAM domain. The DLC2-SAM domain structure reveals an atypical four-helix composition that is distinct from the five-helix SAM domain structures that have been determined to date. From structural alignments, helix 3 of the canonical SAM domain appears to be replaced by shorter, extended secondary structure that follows a similar path. Another difference is demonstrated by helices 1 and 2 that form a helical hairpin that is situated approximately parallel to the canonical helix 5.
The DLC2-SAM domain adopts a structure that is topologically more similar to an anti-parallel four-helix bundle than a canonical SAM domain. This alternate topology may allow the DLC2-SAM domain to interact with a novel set of ligands.

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    • "Several studies suggest that the principal role of SAM domains is to mediate protein-protein and protein-nucleic acid interactions (Kim et al., 2002; Lackmann et al., 1998; Ramachander and Bowie, 2004; Schultz et al., 1997). The structures of a number of isolated SAM domains and of SAM domains in complexes have been solved (Smalla et al., 1999; Stapleton et al., 1999; Thanos et al., 1999a; Thanos et al., 1999b), revealing a relatively well conserved fold consisting of 5 alpha-helices, although some deviations in helix angles, if not limits -and in one case also in the number of helices-have been noted (Kwan and Donaldson, 2007). Several, but far from all SAM domains are known to homodimerize and/or heterodimerize (Ramachander and Bowie, 2004), but the rules for the different behaviors are just emerging (Meruelo and Bowie, 2009). "
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