Validation of Inter-Helical Orientation of the Sterile-α-Motif Domain of the Deleted in Liver Cancer 2 (DLC2-SAM) by 15N-1H Residual Dipolar Couplings

Abstract

Abstract:

The deleted in liver cancer 2 (DLC2), a tumor suppression gene which is frequently found to be underexpressed in hepatocellular carcinoma, encodes a multi-domain protein comprising a sterile- α-motif domain (DLC2-SAM). Previous NMR structural studies of the SAM domain protein (DLC2-SAM) revealed a unique four helical bundle structure, distinct from any other known SAM domain structures. In the present study, we have applied ¹⁵N-¹H residual dipolar couplings as additional constraints to refining the solution structures of the DLC2-SAM together with nuclear Overhauser enhancement and TALOS data. The resulting structures show improved quality factors when comparing with the structures derived without RDC constraints and have a lower Q factor. Orientations of the helices, in particular the helix 4, are validated by residual dipolar coupling data. Our RDC-refined human DLC2-SAM structures resemble those of murine DLC2-SAM. The unique structures of the SAM domain from DLC family implicate that the SAM domain may serve novel functions although these have not yet been unveiled.

Key words: NMR spectroscopy, DLC2, residual dipolar coupling, SAM domain, structure refinement

CLC Number:

O482.53

LI Hong-Yan, SZE Kong-Hung, FUNG King-Leung, SUN Gong-Zhe. Validation of Inter-Helical Orientation of the Sterile-α-Motif Domain of the Deleted in Liver Cancer 2 (DLC2-SAM) by ¹⁵N-¹H Residual Dipolar Couplings[J]. Chinese Journal of Magnetic Resonance, 2010, 27(4): 584-596.

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Validation of Inter-Helical Orientation of the Sterile-α-Motif Domain of the Deleted in Liver Cancer 2 (DLC2-SAM) by ¹⁵N-¹H Residual Dipolar Couplings

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