6cbe

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Revision as of 07:57, 29 August 2018

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Atomic structure of a rationally engineered gene delivery vector, AAV2.5

Structural highlights

6cbe is a 60 chain structure with sequence from Aav-2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	VP1 (AAV-2)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Warning: this is a large structure, and loading might take a long time or not happen at all.

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

AAV2.5 represents the first structure-guided in-silico designed Adeno-associated virus (AAV) gene delivery vector. This engineered vector combined the receptor attachment properties of AAV serotype 2 (AAV2) with the muscle tropic properties of AAV1, and exhibited an antibody escape phenotype because of a modified antigenic epitope. To confirm the design, the structure of the vector was determined to a resolution of 2.78A using cryo-electron microscopy and image reconstruction. The structure of the major viral protein (VP), VP3, was ordered from residue 219 to 736, as reported for other AAV structures, and the five AAV2.5 residues exchanged from AAV2 to AAV1, Q263A, T265 (insertion), N706A, V709A, and T717N, were readily interpretable. Significantly, the surface loops containing these residues adopt the AAV1 conformation indicating the importance of amino acid residues in dictating VP structure.

Atomic structure of a rationally engineered gene delivery vector, AAV2.5.,Burg M, Rosebrough C, Drouin LM, Bennett A, Mietzsch M, Chipman P, McKenna R, Sousa D, Potter M, Byrne B, Jude Samulski R, Agbandje-McKenna M J Struct Biol. 2018 May 18. pii: S1047-8477(18)30119-9. doi:, 10.1016/j.jsb.2018.05.004. PMID:29775653^[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
↑ Burg M, Rosebrough C, Drouin LM, Bennett A, Mietzsch M, Chipman P, McKenna R, Sousa D, Potter M, Byrne B, Jude Samulski R, Agbandje-McKenna M. Atomic structure of a rationally engineered gene delivery vector, AAV2.5. J Struct Biol. 2018 May 18. pii: S1047-8477(18)30119-9. doi:, 10.1016/j.jsb.2018.05.004. PMID:29775653 doi:http://dx.doi.org/10.1016/j.jsb.2018.05.004

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6cbe"

@@ Line 3: / Line 3: @@
 <StructureSection load='6cbe' size='340' side='right' caption='[[6cbe]], [[Resolution|resolution]] 2.78&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6cbe]] is a 60 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6CBE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CBE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6cbe]] is a 60 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=6CBE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6CBE FirstGlance]. <br>
-</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=6cbe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cbe OCA], [http://pdbe.org/6cbe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cbe RCSB], [http://www.ebi.ac.uk/pdbsum/6cbe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cbe ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10804 AAV-2])</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=6cbe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cbe OCA], [http://pdbe.org/6cbe PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cbe RCSB], [http://www.ebi.ac.uk/pdbsum/6cbe PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cbe ProSAT]</span></td></tr>
 </table>
 {{Large structure}}
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Aav-2]]
 [[Category: Agbandje-McKenna, M]]
 [[Category: Bennett, A]]

6cbe

From Proteopedia

Revision as of 07:57, 29 August 2018

Atomic structure of a rationally engineered gene delivery vector, AAV2.5

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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