Novel Adiponectin Variants Identified in Type 2 Diabetic Patients Reveal Multimerization and Secretion Defects 英文参考文献.docVIP
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Novel Adiponectin Variants Identified in Type 2 Diabetic Patients Reveal Multimerization and Secretion Defects 英文参考文献
NovelAdiponectinVariantsIdentifiedinType2Diabetic
PatientsRevealMultimerizationandSecretionDefects
PrapapornJungtrakoon1.,NattachetPlengvidhya2.,WatipTangjittipokin1,SarinChimnaronk3 ,Wanisa
Salaemae1,NalineeChongjaroen1,KanjanaChanprasert1,JatupornSujjitjoon1,ChatchawanSrisawat4,
Pa-thaiYenchitsomanus5*
1DepartmentofImmunology,FacultyofMedicineSirirajHospital,MahidolUniversity,Bangkok,Thailand,2DivisionofEndocrinologyandMetabolism,Departmentof
Medicine,FacultyofMedicineSirirajHospital,MahidolUniversity,Bangkok,Thailand,3InstituteofMolecularBiosciences,MahidolUniversity,Nakhonpathom,Thailand,
4Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, 5Division of Medical Molecular Biology, Department of
ResearchandDevelopment,FacultyofMedicineSirirajHospital,MahidolUniversity,Bangkok,Thailand
Abstract
ADIPOQ,encodingadiponectin,isacandidategenefortype2diabetes(T2D)identifiedbygenome-widelinkageanalyses
with supporting evidence showing the protein function in sensitizing insulin actions. In an endeavor to characterize
candidate genes causing T2D in Thai patients, we identified 10 novel ADIPOQ variations, several of which were non-
synonymous variations observed only in the patients. To examine the impact of these non-synonymous variations on
adiponectin structure and biochemical characteristics, we conducted a structural analysis of the wild-type and variant
proteins by in silico modeling and further characterized biochemical properties of the variants with predicted structural
abnormalitiesfromthemodelingbymolecularandbiochemicalstudies.Therecombinantplasmidscontainingwild-type
andvariantADIPOQcDNAsderivedfromthevariationsidentifiedbyourstudy(R55H,R112H,andR131H)andpreviouswork
(G90SandR112C)wereconstructedandtransientlyexpressedandco-expressedinculturedHEK293Tcellstoinvestigate
theiroligomerization,interaction,andsecretion.WefoundthatthenovelR55Hvariantimpairedproteinmultimerization
butitdidnotexerttheeffectovertheco
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