2h80
From Proteopedia
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NMR structures of SAM domain of Deleted in Liver Cancer 2 (DLC2)
Overview
The deleted in liver cancer 2 (DLC2) is a tumor suppressor gene, frequently found to be underexpressed in hepatocellular carcinoma. DLC2 is, a multidomain protein containing a sterile alpha-motif (SAM) domain, a, GTPase-activating protein (GAP) domain, and a lipid-binding StAR-related, lipid-transfer (START) domain. The SAM domain of DLC2, DLC2-SAM, exhibits, a low level of sequence homology (15-30%) with other SAM domains, and, appears to be the prototype of a new subfamily of SAM domains found in, DLC2-related proteins. In the present study, we have determined the, three-dimensional solution structure of DLC2-SAM using NMR methods, together with molecular dynamics simulated annealing. In addition, we, performed a backbone dynamics study. The DLC2-SAM packed as a unique four, alpha-helical bundle stabilized by interhelix hydrophobic interactions., The arrangement of the four helices is distinct from all other known SAM, domains. In contrast to some members of the SAM domain family which form, either dimers or oligomers, both biochemical analyses and rotational, correlation time (tau(c)) measured by backbone 15N relaxation experiments, indicated that DLC2-SAM exists as a monomer in solution. The interaction, of DLC2-SAM domain with sodium dodecyl sulfate (SDS) micelles and, 1,2-dimyristoyl-sn-glycerol-3-phosphatidylglycerol (DMPG) phospholipids, was examined by CD and NMR spectroscopic techniques. The DLC2-SAM exhibits, membrane binding properties accompanied by minor loss of the secondary, structure of the protein. Deletion studies showed that the, self-association of DLC2 in vivo does not require SAM domain, instead, a, protein domain consisting of residues 120-672 mediates the, self-association of DLC2.
About this Structure
2H80 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Solution structures, dynamics, and lipid-binding of the sterile alpha-motif domain of the deleted in liver cancer 2., Li H, Fung KL, Jin DY, Chung SS, Ching YP, Ng IO, Sze KH, Ko BC, Sun H, Proteins. 2007 Jun 1;67(4):1154-66. PMID:17380510
Page seeded by OCA on Wed Jan 23 15:16:17 2008
