Staff View
Crystal structure of Sindbis virus precursor form of nonstructural protein 2/3

Descriptive

TypeOfResource
Text
TitleInfo (ID = T-1)
Title
Crystal structure of Sindbis virus precursor form of nonstructural protein 2/3
Identifier
ETD_2889
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000056774
Language
LanguageTerm (authority = ISO639-2); (type = code)
eng
Genre (authority = marcgt)
theses
Subject (ID = SBJ-1); (authority = RUETD)
Topic
Biochemistry
Subject (ID = SBJ-2); (authority = ETD-LCSH)
Topic
RNA viruses--Research
Abstract (type = abstract)
Alphaviruses are a globally distributed group of enveloped, positive-sense RNA animal viruses. The 5’ two-thirds of the RNA genome is translated into a single, large polypeptide of ~2500 amino acids. This polypeptide is autoproteolytically cleaved into four subunits, termed nonstructural proteins (nsP) 1-4, which form the replication complex. The nsP1 is the enzyme responsible for capping the viral mRNA and a membrane associated protein. The nsP2 has RNA helicase, triphosphatase activities and is an autoprotease responsible for cleaving the nonstructural polyprotein. The nsP4 is an RNA-dependent, RNA polymerase. The function of nsP3 remains unknown, however, it is the only viral protein phosphorylated by unknown cellular kinases. The nsP3 contains a macro or X domain that binds ADP-ribose and is highly conserved with homologues in rubella virus, hepatitis E virus and coronaviruses, including severe acute respiratory syndrome (SARS) virus. The protease domain of viral nsP2 protein cleaves the nsP1234 polyprotein replication complex into functional proteins. During replication of alphavirus genome, the positive strand of RNA genome is transcribed into a minus strand by the cleavage intermediate nsP123 and nsP4. Cleavage between nsP2/3 causes a template switch from minus strand to positive strand. Although the nonstructural protein 2/3 is essential for RNA replication, its function in viral replication is still not well understood. Here we report the crystal structure of Sindbis virus precursor form of nsP2/3 at 2.94Å resolution. The structure of Sindbis nsP2/3 protein consists of four distinct domains, which are the protease domain, methyltransferase like domain, macro domain and zinc binding domain. Surprisingly, nsP3 contains a novel folding with a previously uncharacterized zinc coordination site. In addition, the cleavage site between nsP2 and nsP3 is buried the two proteins and not accessible for proteolysis. Furthermore, the loop connecting the macro and zinc-binding domains makes direct contact with and causes a structure shift in the nsp2 protease domain. We have observed considerable differences between the pre-cleavage and post-cleavage forms of nsp2/3. The structure suggests that a conformational change in nsP2/3 is required in order for the nsP2 protease to gain access to the nsP2/3 cleavage site.
PhysicalDescription
Form (authority = gmd)
electronic resource
Extent
vii, 42 p. : ill.
InternetMediaType
application/pdf
InternetMediaType
text/xml
Note (type = degree)
M.S.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Gye Hwa Shin
Name (ID = NAME-1); (type = personal)
NamePart (type = family)
Shin
NamePart (type = given)
Gyehwa
NamePart (type = date)
1975-
Role
RoleTerm (authority = RULIB)
author
DisplayForm
Gyehwa Shin
Name (ID = NAME-2); (type = personal)
NamePart (type = family)
Marcotrigiano
NamePart (type = given)
Joe
Role
RoleTerm (authority = RULIB)
chair
Affiliation
Advisory Committee
DisplayForm
Joe Marcotrigiano
Name (ID = NAME-3); (type = personal)
NamePart (type = family)
Gabriel
NamePart (type = given)
Abram
Role
RoleTerm (authority = RULIB)
internal member
Affiliation
Advisory Committee
DisplayForm
Abram Gabriel
Name (ID = NAME-4); (type = personal)
NamePart (type = family)
Nanda
NamePart (type = given)
Vikas
Role
RoleTerm (authority = RULIB)
internal member
Affiliation
Advisory Committee
DisplayForm
Vikas Nanda
Name (ID = NAME-1); (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (ID = NAME-2); (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
OriginInfo
DateCreated (qualifier = exact)
2010
DateOther (qualifier = exact); (type = degree)
2010-10
Place
PlaceTerm (type = code)
xx
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3NV9J0N
Genre (authority = ExL-Esploro)
ETD graduate
Back to the top

Rights

RightsDeclaration (AUTHORITY = GS); (ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder (ID = PRH-1); (type = personal)
Name
FamilyName
Shin
GivenName
Gyehwa
Role
Copyright Holder
RightsEvent (AUTHORITY = rulib); (ID = RE-1)
Type
Permission or license
DateTime
2010-09-21 23:27:07
AssociatedEntity (AUTHORITY = rulib); (ID = AE-1)
Role
Copyright holder
Name
Gyehwa Shin
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject (AUTHORITY = rulib); (ID = AO-1)
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent (AUTHORITY = rulib); (ID = RE-2)
Type
Embargo
DateTime
2011-01-18
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 30th, 2012.
Back to the top

Technical

ContentModel
ETD
MimeType (TYPE = file)
application/pdf
MimeType (TYPE = container)
application/x-tar
FileSize (UNIT = bytes)
3758080
Checksum (METHOD = SHA1)
979184e5a8203ce4c79962327823808066d27d4f
Back to the top
Version 8.3.13
Rutgers University Libraries - Copyright ©2021