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1lp3

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Revision as of 12:25, 13 November 2019

The Atomic Structure of Adeno-Associated Virus (AAV-2), a Vector for Human Gene Therapy

Structural highlights

1lp3 is a 1 chain structure with sequence from Aav-2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CAPSD_AAV2S] Capsid protein self-assembles to form an icosahedral capsid with a T=1 symmetry, about 22 nm in diameter, and consisting of 60 copies of three size variants of the capsid protein VP1, VP2 and VP3 which differ in their N-terminus. The capsid encapsulates the genomic ssDNA. Binds to host cell heparan sulfate and uses host ITGA5-ITGB1 as coreceptor on the cell surface to provide virion attachment to target cell. This attachment induces virion internalization predominantly through clathrin-dependent endocytosis. Binding to the host receptor also induces capsid rearrangements leading to surface exposure of VP1 N-terminus, specifically its phospholipase A2-like region and putative nuclear localization signal(s). VP1 N-terminus might serve as a lipolytic enzyme to breach the endosomal membrane during entry into host cell and might contribute to virus transport to the nucleus.^[1] ^[2] ^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The structure of the adeno-associated virus (AAV-2) has been determined to 3-A resolution by x-ray crystallography. AAV is being developed as a vector for gene therapy to treat diseases including hemophilia, cancer, and cystic fibrosis. As in the distantly related autonomous parvoviruses, the capsid protein has a beta-barrel fold, but long loops between the beta-strands share little structural homology with other parvoviruses, leading to unique surface features. Most prominent are groups of threefold-related peaks, each an intimate association of loops from two neighboring subunits. Mutations affecting cell entry and receptor binding are clustered near the positively charged side of each peak, implicating the region in attachment to the cellular receptor, heparan sulfate proteoglycan. Amino acids involved in antibody binding are in the same general vicinity. The structure will guide rational engineering of vector capsids to tailor cellular targeting and to avoid immediate neutralization by an immune system sensitized by prior exposure to AAV.

The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy.,Xie Q, Bu W, Bhatia S, Hare J, Somasundaram T, Azzi A, Chapman MS Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10405-10. Epub 2002 Jul 22. PMID:12136130^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bartlett JS, Wilcher R, Samulski RJ. Infectious entry pathway of adeno-associated virus and adeno-associated virus vectors. J Virol. 2000 Mar;74(6):2777-85. PMID:10684294
↑ Girod A, Wobus CE, Zadori Z, Ried M, Leike K, Tijssen P, Kleinschmidt JA, Hallek M. The VP1 capsid protein of adeno-associated virus type 2 is carrying a phospholipase A2 domain required for virus infectivity. J Gen Virol. 2002 May;83(Pt 5):973-8. PMID:11961250
↑ Asokan A, Hamra JB, Govindasamy L, Agbandje-McKenna M, Samulski RJ. Adeno-associated virus type 2 contains an integrin alpha5beta1 binding domain essential for viral cell entry. J Virol. 2006 Sep;80(18):8961-9. PMID:16940508 doi:http://dx.doi.org/10.1128/JVI.00843-06
↑ Summerford C, Samulski RJ. Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol. 1998 Feb;72(2):1438-45. PMID:9445046
↑ Xie Q, Bu W, Bhatia S, Hare J, Somasundaram T, Azzi A, Chapman MS. The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10405-10. Epub 2002 Jul 22. PMID:12136130 doi:http://dx.doi.org/10.1073/pnas.162250899

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1lp3"

@@ Line 1: / Line 1: @@
 ==The Atomic Structure of Adeno-Associated Virus (AAV-2), a Vector for Human Gene Therapy==
-<StructureSection load='1lp3' size='340' side='right' caption='[[1lp3]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
+<StructureSection load='1lp3' size='340' side='right'caption='[[1lp3]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[1lp3]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aav-2 Aav-2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LP3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1LP3 FirstGlance]. <br>
@@ Line 27: / Line 27: @@
 </div>
 <div class="pdbe-citations 1lp3" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Virus coat protein|Virus coat protein]]
 == References ==
 <references/>
@@ Line 32: / Line 35: @@
 </StructureSection>
 [[Category: Aav-2]]
+[[Category: Large Structures]]
 [[Category: Azzi, A]]
 [[Category: Bhatia, S]]

1lp3

From Proteopedia

Revision as of 12:25, 13 November 2019

The Atomic Structure of Adeno-Associated Virus (AAV-2), a Vector for Human Gene Therapy

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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