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


CONCLUSIONS
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.
Kwan
Jamie J
JJ
Department of Biology, York University, Toronto, Ontario, Canada. jkwan@yorku.ca <jkwan@yorku.ca>
Donaldson
Logan W
LW
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D005091:Exons; D006639:Histidine / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013059:Spectrum Analysis, Raman; D025521:Tumor Suppressor Proteins / Q000032:analysis* / Q000737:chemistry
D006639:Histidine; D025521:Tumor Suppressor Proteins; C473606:Stard13 protein, mouse