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Article: Homophilic adhesion of human CEACAM1 involves N-terminal domain interactions: Structural analysis of the binding site

TitleHomophilic adhesion of human CEACAM1 involves N-terminal domain interactions: Structural analysis of the binding site
Authors
Issue Date2001
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
Citation
Blood, 2001, v. 98 n. 5, p. 1469-1479 How to Cite?
AbstractCEACAM1 on leukocytic, endothelial, and epithelial cells functions in homophilic adhesion, tumor suppression, regulating cell adhesion and proliferation, and in heterophilic adhesion as a receptor for E-selectin and Neisseria meningiditis, Neisseria gonorrhoeae, Haemophilus influenzae, and murine coronaviruses. The 8 transmembrane isoforms of human CEACAM1 possess an extracellular N-terminal IgV domain, followed by variable numbers of IgC2 domains. To establish which key amino acids contribute specifically to CEACAM1 homophilic adhesion, exposed amino acids in the N-terminal domain of a soluble form of CEACAM1 were subjected to mutagenesis. Analyses of mutant proteins with conformationally dependent antibodies indicated that most mutations did not substantially affect the structural integrity of CEACAM1. Nevertheless, decreased adhesion was observed for the single mutants V39A or D40A (single-letter amino acid codes) in the CC′ loop and for the triple mutants located in the GFCC′C″ face of the N-terminal domain. Interestingly, whereas single mutations in R64 or D82 that are predicted to form a salt bridge between the base of the D and F β strands close to the critical V39 and D40 residues also abolish adhesion, an amino acid swap (R64D and D82R), which maintains the salt bridge was without significant effect. These studies indicate that the CC′ loop plays a crucial role in the homophilic adhesion of CEACAM1. They further predict that specific hydrophobic amino acid residues on the nonglycosylated GFCC′C″ face of CEACAM1 N-terminal domain are not only involved in heterophilic interactions with Opa proteins and H influenzae, but are also critical for protein-protein interactions between 2 CEACAM1 molecules on opposing cells. © 2001 by The American Society of Hematology.
Persistent Identifierhttp://hdl.handle.net/10722/170035
ISSN
2015 Impact Factor: 11.841
2015 SCImago Journal Rankings: 6.395
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWatt, SMen_US
dc.contributor.authorTeixeira, AMen_US
dc.contributor.authorZhou, GQen_US
dc.contributor.authorDoyonnas, Ren_US
dc.contributor.authorZhang, Yen_US
dc.contributor.authorGrunert, Fen_US
dc.contributor.authorBlumberg, RSen_US
dc.contributor.authorKuroki, Men_US
dc.contributor.authorSkubitz, KMen_US
dc.contributor.authorBates, PAen_US
dc.date.accessioned2012-10-30T06:04:52Z-
dc.date.available2012-10-30T06:04:52Z-
dc.date.issued2001en_US
dc.identifier.citationBlood, 2001, v. 98 n. 5, p. 1469-1479en_US
dc.identifier.issn0006-4971en_US
dc.identifier.urihttp://hdl.handle.net/10722/170035-
dc.description.abstractCEACAM1 on leukocytic, endothelial, and epithelial cells functions in homophilic adhesion, tumor suppression, regulating cell adhesion and proliferation, and in heterophilic adhesion as a receptor for E-selectin and Neisseria meningiditis, Neisseria gonorrhoeae, Haemophilus influenzae, and murine coronaviruses. The 8 transmembrane isoforms of human CEACAM1 possess an extracellular N-terminal IgV domain, followed by variable numbers of IgC2 domains. To establish which key amino acids contribute specifically to CEACAM1 homophilic adhesion, exposed amino acids in the N-terminal domain of a soluble form of CEACAM1 were subjected to mutagenesis. Analyses of mutant proteins with conformationally dependent antibodies indicated that most mutations did not substantially affect the structural integrity of CEACAM1. Nevertheless, decreased adhesion was observed for the single mutants V39A or D40A (single-letter amino acid codes) in the CC′ loop and for the triple mutants located in the GFCC′C″ face of the N-terminal domain. Interestingly, whereas single mutations in R64 or D82 that are predicted to form a salt bridge between the base of the D and F β strands close to the critical V39 and D40 residues also abolish adhesion, an amino acid swap (R64D and D82R), which maintains the salt bridge was without significant effect. These studies indicate that the CC′ loop plays a crucial role in the homophilic adhesion of CEACAM1. They further predict that specific hydrophobic amino acid residues on the nonglycosylated GFCC′C″ face of CEACAM1 N-terminal domain are not only involved in heterophilic interactions with Opa proteins and H influenzae, but are also critical for protein-protein interactions between 2 CEACAM1 molecules on opposing cells. © 2001 by The American Society of Hematology.en_US
dc.languageengen_US
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/en_US
dc.relation.ispartofBlooden_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntibodies, Monoclonal - Immunologyen_US
dc.subject.meshAntigens, Cd - Chemistry - Genetics - Immunology - Physiologyen_US
dc.subject.meshAntigens, Differentiation - Chemistry - Genetics - Immunology - Physiologyen_US
dc.subject.meshBinding Sitesen_US
dc.subject.meshCho Cellsen_US
dc.subject.meshCarcinoembryonic Antigen - Classificationen_US
dc.subject.meshCell Adhesion - Physiologyen_US
dc.subject.meshCell Adhesion Moleculesen_US
dc.subject.meshCricetinaeen_US
dc.subject.meshCricetulusen_US
dc.subject.meshEpitopes - Immunologyen_US
dc.subject.meshHumansen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMultigene Familyen_US
dc.subject.meshMutagenesis, Site-Directeden_US
dc.subject.meshOrgan Specificityen_US
dc.subject.meshProtein Conformationen_US
dc.subject.meshProtein Isoforms - Chemistry - Genetics - Immunology - Physiologyen_US
dc.subject.meshProtein Structure, Tertiaryen_US
dc.subject.meshRecombinant Fusion Proteins - Chemistry - Physiologyen_US
dc.subject.meshSequence Alignmenten_US
dc.subject.meshSequence Homology, Amino Aciden_US
dc.subject.meshStructure-Activity Relationshipen_US
dc.titleHomophilic adhesion of human CEACAM1 involves N-terminal domain interactions: Structural analysis of the binding siteen_US
dc.typeArticleen_US
dc.identifier.emailZhou, GQ:wormoscz@gmail.comen_US
dc.identifier.authorityZhou, GQ=rp00527en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1182/blood.V98.5.1469en_US
dc.identifier.pmid11520797-
dc.identifier.scopuseid_2-s2.0-0035469860en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035469860&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume98en_US
dc.identifier.issue5en_US
dc.identifier.spage1469en_US
dc.identifier.epage1479en_US
dc.identifier.isiWOS:000170685000029-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridWatt, SM=7102659490en_US
dc.identifier.scopusauthoridTeixeira, AM=7202385471en_US
dc.identifier.scopusauthoridZhou, GQ=23394245100en_US
dc.identifier.scopusauthoridDoyonnas, R=6602247912en_US
dc.identifier.scopusauthoridZhang, Y=8918992000en_US
dc.identifier.scopusauthoridGrunert, F=7003755998en_US
dc.identifier.scopusauthoridBlumberg, RS=7102990864en_US
dc.identifier.scopusauthoridKuroki, M=7101912810en_US
dc.identifier.scopusauthoridSkubitz, KM=7006006597en_US
dc.identifier.scopusauthoridBates, PA=7201982123en_US

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