145 273

Cited 0 times in

Determination of encephalomyocarditis viral diabetogenicity by a putative binding site of the viral capsid protein.

Authors
Jun, HS; Kang, Y; Yoon, HS; Kim, KH; Notkins, AL; Yoon, JW
Citation
Diabetes, 47(4):576-582, 1998
Journal Title
Diabetes
ISSN
0012-17971939-327X
Abstract
The molecular mechanism by which some, but not all, variants of encephalomyocarditis (EMC) virus selectively infect pancreatic beta-cells in mice and induce IDDM has been an enigma for more than a decade. We report here that the binding site of the EMC viral capsid protein VP1 determines viral diabetogenicity. Recombinant chimeric EMC viruses containing threonine, serine, proline, aspartic acid, or valine at position 152 of the major capsid protein VP1 bind poorly to beta-cells. In contrast, recombinant chimeric EMC viruses containing alanine or glycine at position 152 of the VP1 bind efficiently to and infect beta-cells, resulting in the development of diabetes. Three-dimensional molecular modeling reveals that the van der Waals interactions are greater and the residues surrounding position 152 of the VP1 are more closely packed in recombinant chimeric viruses containing threonine, serine, proline, aspartic acid, or valine at position 152 than in recombinant chimeric viruses containing alanine or glycine at the same position. Our studies reveal that the surface areas surrounding alanine or glycine at position 152 of the VP1 are more accessible, thus increasing the availability of the binding sites for attachment to beta-cell receptors and resulting in viral infection and the development of diabetes.
MeSH terms
AnimalsBinding SitesCapsid/chemistry/genetics/*metabolism*Capsid ProteinsDiabetes Mellitus, Type 1/metabolism/*virologyEncephalomyocarditis virus/genetics/metabolism/*pathogenicityIslets of Langerhans/metabolism/virologyMaleMiceModels, MolecularPoint MutationProtein ConformationRecombination, Genetic
PMID
9568690
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
AJOU Authors
강, 엽윤, 지원
Full Text Link
Files in This Item:
576.full.pdfDownload
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse