3j1s

From Proteopedia

(Difference between revisions)

Revision as of 17:43, 10 April 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 3: / Line 3: @@
 <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>
+<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://proteopedia.org/fgij/fg.htm?mol=3J1S FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1lp3|1lp3]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3j1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j1s OCA], [http://pdbe.org/3j1s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3j1s RCSB], [http://www.ebi.ac.uk/pdbsum/3j1s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3j1s ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=3j1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j1s OCA], [http://pdbe.org/3j1s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3j1s RCSB], [http://www.ebi.ac.uk/pdbsum/3j1s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3j1s ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 21: @@
 ==See Also==
 *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
-*[[Virus coat protein|Virus coat protein]]
+*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
 == References ==
 <references/>

3j1s

From Proteopedia

Revision as of 17:43, 10 April 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?)

Views

Personal tools

Navigation

Search

Toolbox