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

source: BMC Structural Biology 2007, 7:34

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*
Address: Department of Biology, York University, 4700 Keele Street, Toronto, Ontario M3J 1P3, Canada
Email: Jamie J Kwan - jkwan@yorku.ca; Logan W Donaldson* - logand@yorku.ca
* Corresponding author

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.