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

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.

A Nuclear Localization Signal at the SAM–SAM Domain Interface of AIDA-1 Suggests a Requirement for Domain Uncoupling Prior to Nuclear Import

“…While most SAM domains employ five helices, the DLC1/2 class of SAM domains has only four helices and an extended region substituting for the third helix. 18,19 Several SAM domains have been observed to bind other SAM domains in both homoand heterotypic modes. A selection of SAM-SAM interactions is shown in Fig.…”

Rho regulation: DLC proteins in space and time

“…Isoforms lacking the SAM domain have been reported for DLC2 and DLC3 [10,16]. SAM domains are typically arranged in five helices but distinct from this, the DLC2 SAM motif forms a four-alpha helical bundle [42,45]. SAM domains occur in many transcription factors and signaling proteins.…”

NMR Structure of a Heterodimeric SAM:SAM Complex: Characterization and Manipulation of EphA2 Binding Reveal New Cellular Functions of SHIP2

“…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).…”