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Article: Solution structures, dynamics, and lipid-binding of the sterile α-motif domain of the deleted in liver cancer 2

TitleSolution structures, dynamics, and lipid-binding of the sterile α-motif domain of the deleted in liver cancer 2
Authors
KeywordsDeleted in liver cancer 2
Lipid-binding
NMR
Sterile α-motif (SAM)
Structures
Issue Date2007
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/36176
Citation
Proteins: Structure, Function And Genetics, 2007, v. 67 n. 4, p. 1154-1166 How to Cite?
AbstractThe 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 α-motif (SARI) 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 α-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 dinners or oligomers, both biochemical analyses and rotational correlation time (τc) 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 SARI domain, instead, a protein domain consisting of residues 120-672 mediates the self-association of DLC2. © 2007 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/147561
ISSN
2015 Impact Factor: 2.499
2015 SCImago Journal Rankings: 1.383
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Hen_HK
dc.contributor.authorFung, KLen_HK
dc.contributor.authorJin, DYen_HK
dc.contributor.authorChung, SSMen_HK
dc.contributor.authorChing, YPen_HK
dc.contributor.authorNg, IOLen_HK
dc.contributor.authorSze, KHen_HK
dc.contributor.authorKo, BCBen_HK
dc.contributor.authorSun, Hen_HK
dc.date.accessioned2012-05-29T06:04:36Z-
dc.date.available2012-05-29T06:04:36Z-
dc.date.issued2007en_HK
dc.identifier.citationProteins: Structure, Function And Genetics, 2007, v. 67 n. 4, p. 1154-1166en_HK
dc.identifier.issn0887-3585en_HK
dc.identifier.urihttp://hdl.handle.net/10722/147561-
dc.description.abstractThe 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 α-motif (SARI) 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 α-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 dinners or oligomers, both biochemical analyses and rotational correlation time (τc) 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 SARI domain, instead, a protein domain consisting of residues 120-672 mediates the self-association of DLC2. © 2007 Wiley-Liss, Inc.en_HK
dc.languageengen_US
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/36176en_HK
dc.relation.ispartofProteins: Structure, Function and Geneticsen_HK
dc.subjectDeleted in liver cancer 2en_HK
dc.subjectLipid-bindingen_HK
dc.subjectNMRen_HK
dc.subjectSterile α-motif (SAM)en_HK
dc.subjectStructuresen_HK
dc.subject.meshAmino Acid Motifsen_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshCircular Dichroismen_US
dc.subject.meshMicellesen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshNuclear Magnetic Resonance, Biomolecularen_US
dc.subject.meshPhospholipids - Chemistry - Metabolismen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshProtein Structure, Tertiaryen_US
dc.subject.meshSequence Alignmenten_US
dc.subject.meshSequence Homology, Amino Aciden_US
dc.subject.meshSodium Dodecyl Sulfateen_US
dc.subject.meshSolutions - Chemistryen_US
dc.subject.meshTumor Suppressor Proteins - Chemistry - Genetics - Metabolismen_US
dc.titleSolution structures, dynamics, and lipid-binding of the sterile α-motif domain of the deleted in liver cancer 2en_HK
dc.typeArticleen_HK
dc.identifier.emailJin, DY: dyjin@hku.hken_HK
dc.identifier.emailChung, SSM: smchung@hkucc.hku.hken_HK
dc.identifier.emailChing, YP: ypching@hku.hken_HK
dc.identifier.emailNg, IOL: iolng@hku.hken_HK
dc.identifier.emailSze, KH: khsze@hku.hken_HK
dc.identifier.emailSun, H: hsun@hku.hken_HK
dc.identifier.authorityJin, DY=rp00452en_HK
dc.identifier.authorityChung, SSM=rp00376en_HK
dc.identifier.authorityChing, YP=rp00469en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.identifier.authoritySze, KH=rp00785en_HK
dc.identifier.authoritySun, H=rp00777en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1002/prot.21361en_HK
dc.identifier.pmid17380510-
dc.identifier.scopuseid_2-s2.0-34248574289en_HK
dc.identifier.hkuros132716-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-34248574289&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume67en_HK
dc.identifier.issue4en_HK
dc.identifier.spage1154en_HK
dc.identifier.epage1166en_HK
dc.identifier.isiWOS:000246415700033-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLi, H=14023043100en_HK
dc.identifier.scopusauthoridFung, KL=7202935039en_HK
dc.identifier.scopusauthoridJin, DY=7201973614en_HK
dc.identifier.scopusauthoridChung, SSM=14120761600en_HK
dc.identifier.scopusauthoridChing, YP=7005431277en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK
dc.identifier.scopusauthoridSze, KH=7006735061en_HK
dc.identifier.scopusauthoridKo, BCB=7102833927en_HK
dc.identifier.scopusauthoridSun, H=7404827446en_HK
dc.identifier.citeulike3813689-

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