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Open Access Research article

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

Jamie J Kwan and Logan W Donaldson*

Author Affiliations

Department of Biology, York University, 4700 Keele Street, Toronto, Ontario M3J 1P3, Canada

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BMC Structural Biology 2007, 7:34  doi:10.1186/1472-6807-7-34

Published: 22 May 2007

Abstract

Background

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.

Results

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.

Conclusion

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.