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Article: Crystal structure of the Mp1p ligand binding domain 2 reveals its function as a fatty acid-binding protein

TitleCrystal structure of the Mp1p ligand binding domain 2 reveals its function as a fatty acid-binding protein
Authors
Issue Date2010
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2010, v. 285 n. 12, p. 9211-9220 How to Cite?
AbstractPenicillium marneffei is a dimorphic, pathogenic fungus in Southeast Asia that mostly afflicts immunocompromised individuals. As the only dimorphic member of the genus, it goes through a phase transition from a mold to yeast form, which is believed to be a requisite for its pathogenicity. Mp1p, a cell wall antigenic mannoprotein existing widely in yeast, hyphae, and conidia of the fungus, plays a vital role in host immune response during infection. To understand the function of Mp1p, we have determined the x-ray crystal structure of its ligand binding domain 2 (LBD2) to 1.3 Å. The structure reveals a dimer between the two molecules. The dimer interface forms a ligand binding cavity, in which electron density was observed for a palmitic acid molecule interacting with LBD2 indirectly through hydrogen bonding networks via two structural water molecules. Isothermal titration calorimetry experiments measured the ligand binding affinity (K d) of Mp1p at the micromolar level. Mutations of ligand-binding residues, namely S313A and S332A, resulted in a 9-fold suppression of ligand binding affinity. Analytical ultracentrifugation assays demonstrated that both LBD2 and Mp1p are mostly monomeric in vitro, no matter with or without ligand, and our dimeric crystal structure of LBD2 might be the result of crystal packing. Based on the conformation of the ligand-binding pocket in the dimer structure, a model for the closed, monomeric form of LBD2 is proposed. Further structural analysis indicated the biological importance of fatty acid binding of Mp1p for the survival and pathogenicity of the conditional pathogen. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/157584
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
Funding AgencyGrant Number
Ministry of Science and Technology 973006CB10901
2007CB914301
863 Project2006AA02A322
International Cooperation Project2006DFB32420
Funding Information:

This work was supported by Ministry of Science and Technology 973 Project Grants 2006CB10901 and 2007CB914301) and 863 Project Grant 2006AA02A322, and International Cooperation Project Grant 2006DFB32420.

References

 

DC FieldValueLanguage
dc.contributor.authorLiao, Sen_US
dc.contributor.authorTung, ETKen_US
dc.contributor.authorZheng, Wen_US
dc.contributor.authorChong, Ken_US
dc.contributor.authorXu, Yen_US
dc.contributor.authorDai, Pen_US
dc.contributor.authorGuo, Yen_US
dc.contributor.authorBartlam, Men_US
dc.contributor.authorYuen, KYen_US
dc.contributor.authorRao, Zen_US
dc.date.accessioned2012-08-08T08:51:28Z-
dc.date.available2012-08-08T08:51:28Z-
dc.date.issued2010en_US
dc.identifier.citationJournal Of Biological Chemistry, 2010, v. 285 n. 12, p. 9211-9220en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/157584-
dc.description.abstractPenicillium marneffei is a dimorphic, pathogenic fungus in Southeast Asia that mostly afflicts immunocompromised individuals. As the only dimorphic member of the genus, it goes through a phase transition from a mold to yeast form, which is believed to be a requisite for its pathogenicity. Mp1p, a cell wall antigenic mannoprotein existing widely in yeast, hyphae, and conidia of the fungus, plays a vital role in host immune response during infection. To understand the function of Mp1p, we have determined the x-ray crystal structure of its ligand binding domain 2 (LBD2) to 1.3 Å. The structure reveals a dimer between the two molecules. The dimer interface forms a ligand binding cavity, in which electron density was observed for a palmitic acid molecule interacting with LBD2 indirectly through hydrogen bonding networks via two structural water molecules. Isothermal titration calorimetry experiments measured the ligand binding affinity (K d) of Mp1p at the micromolar level. Mutations of ligand-binding residues, namely S313A and S332A, resulted in a 9-fold suppression of ligand binding affinity. Analytical ultracentrifugation assays demonstrated that both LBD2 and Mp1p are mostly monomeric in vitro, no matter with or without ligand, and our dimeric crystal structure of LBD2 might be the result of crystal packing. Based on the conformation of the ligand-binding pocket in the dimer structure, a model for the closed, monomeric form of LBD2 is proposed. Further structural analysis indicated the biological importance of fatty acid binding of Mp1p for the survival and pathogenicity of the conditional pathogen. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.titleCrystal structure of the Mp1p ligand binding domain 2 reveals its function as a fatty acid-binding proteinen_US
dc.typeArticleen_US
dc.identifier.emailYuen, KY:kyyuen@hkucc.hku.hken_US
dc.identifier.authorityYuen, KY=rp00366en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1074/jbc.M109.057760en_US
dc.identifier.pmid20053994-
dc.identifier.scopuseid_2-s2.0-77950574614en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77950574614&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume285en_US
dc.identifier.issue12en_US
dc.identifier.spage9211en_US
dc.identifier.epage9220en_US
dc.identifier.isiWOS:000275553700070-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLiao, S=35785928200en_US
dc.identifier.scopusauthoridTung, ETK=23398349800en_US
dc.identifier.scopusauthoridZheng, W=37032327900en_US
dc.identifier.scopusauthoridChong, K=7102553965en_US
dc.identifier.scopusauthoridXu, Y=7406445588en_US
dc.identifier.scopusauthoridDai, P=55166042500en_US
dc.identifier.scopusauthoridGuo, Y=35785545800en_US
dc.identifier.scopusauthoridBartlam, M=6701775559en_US
dc.identifier.scopusauthoridYuen, KY=36078079100en_US
dc.identifier.scopusauthoridRao, Z=34668339000en_US

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