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3j1s

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Revision as of 17:17, 6 March 2020

Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20

3j1s, resolution 8.50Å

Structural highlights

3j1s is a 3 chain structure with sequence from Adeno-associated virus - 2 and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1lp3
Experimental data:	Check to display Experimental Data
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]

Publication Abstract from PubMed

The use of adeno-associated virus (AAV) as a gene therapy vector is limited by the host neutralizing immune response. The cryo-electron microscopy (EM) structure at 8.5A resolution is determined for a complex of AAV-2 with the Fab' fragment of monoclonal antibody (MAb) A20, the most extensively characterized AAV MAb. The binding footprint is determined through fitting the cryo-EM reconstruction with a homology model following sequencing of the variable domain, and provides a structural basis for integrating diverse prior epitope mappings. The footprint extends from the previously implicated plateau to the side of the spike, and into the conserved canyon, covering a larger area than anticipated. Comparison with structures of binding and non-binding serotypes indicates that recognition depends on a combination of subtle serotype-specific features. Separation of the neutralizing epitope from the heparan sulfate cell attachment site encourages attempts to develop immune-resistant vectors that can still bind to target cells.

Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20.,McCraw DM, O'Donnell JK, Taylor KA, Stagg SM, Chapman MS Virology. 2012 Sep 15;431(1-2):40-9. Epub 2012 Jun 9. PMID:22682774^[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
↑ McCraw DM, O'Donnell JK, Taylor KA, Stagg SM, Chapman MS. Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20. Virology. 2012 Sep 15;431(1-2):40-9. Epub 2012 Jun 9. PMID:22682774 doi:10.1016/j.virol.2012.05.004

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3j1s"

@@ Line 1: / Line 1: @@
 ==Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20==
-<StructureSection load='3j1s' size='340' side='right' caption='[[3j1s]], [[Resolution|resolution]] 8.50&Aring;' scene=''>
+<SX load='3j1s' size='340' side='right' viewer='molstar' caption='[[3j1s]], [[Resolution|resolution]] 8.50&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3j1s]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Adeno-associated_virus_-_2 Adeno-associated virus - 2] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J1S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3J1S FirstGlance]. <br>
@@ Line 25: / Line 25: @@
 <references/>
 __TOC__
-</StructureSection>
+</SX>
 [[Category: Adeno-associated virus - 2]]
+[[Category: Large Structures]]
 [[Category: Mus musculus]]
 [[Category: Chapman, M S]]

3j1s

From Proteopedia

Revision as of 17:17, 6 March 2020

Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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