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6e9d

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Revision as of 21:02, 6 March 2020

Sub-2 Angstrom Ewald Curvature-Corrected Single-Particle Cryo-EM Reconstruction of AAV-2 L336C

6e9d, resolution 1.86Å

Structural highlights

6e9d is a 60 chain structure with sequence from Ade02. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	VP1 (ADE02)
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

Single-particle cryogenic electron microscopy (cryo-EM) provides a powerful methodology for structural biologists, but the resolutions typically attained with experimentally determined structures have lagged behind microscope capabilities. Here, we exploit several technical advances to improve resolution, including per-particle contrast transfer function (CTF) refinement and correction for Ewald sphere curvature. The latter is demonstrated with several experimental samples and should become more standard as resolutions increase or at lower microscope accelerating voltages. The combined application of the described methods to micrographs recorded on a Titan Krios enables structure determination at ~1.86-A resolution of an adeno-associated virus serotype 2 variant (AAV2), an important gene-delivery vehicle. The resulting structural details provide an improved model for understanding the biology of AAV that will guide future vector development for gene therapy.

Sub-2 A Ewald curvature corrected structure of an AAV2 capsid variant.,Tan YZ, Aiyer S, Mietzsch M, Hull JA, McKenna R, Grieger J, Samulski RJ, Baker TS, Agbandje-McKenna M, Lyumkis D Nat Commun. 2018 Sep 7;9(1):3628. doi: 10.1038/s41467-018-06076-6. PMID:30194371^[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
↑ Tan YZ, Aiyer S, Mietzsch M, Hull JA, McKenna R, Grieger J, Samulski RJ, Baker TS, Agbandje-McKenna M, Lyumkis D. Sub-2 A Ewald curvature corrected structure of an AAV2 capsid variant. Nat Commun. 2018 Sep 7;9(1):3628. doi: 10.1038/s41467-018-06076-6. PMID:30194371 doi:http://dx.doi.org/10.1038/s41467-018-06076-6

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/6e9d"

@@ Line 1: / Line 1: @@
 ==Sub-2 Angstrom Ewald Curvature-Corrected Single-Particle Cryo-EM Reconstruction of AAV-2 L336C==
-<StructureSection load='6e9d' size='340' side='right'caption='[[6e9d]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
+<SX load='6e9d' size='340' side='right' viewer='molstar' caption='[[6e9d]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6e9d]] is a 60 chain structure with sequence from [http://en.wikipedia.org/wiki/Ade02 Ade02]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E9D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E9D FirstGlance]. <br>
@@ Line 21: / Line 21: @@
 <references/>
 __TOC__
-</StructureSection>
+</SX>
 [[Category: Ade02]]
 [[Category: Large Structures]]

6e9d

From Proteopedia

Revision as of 21:02, 6 March 2020

Sub-2 Angstrom Ewald Curvature-Corrected Single-Particle Cryo-EM Reconstruction of AAV-2 L336C

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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