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6ihb

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Revision as of 22:08, 6 March 2020

Adeno-Associated Virus 2 in complex with AAVR

6ihb, resolution 2.84Å

Structural highlights

6ihb is a 2 chain structure with sequence from Adeno-associated virus 2 (isolate srivastava/1982) and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	KIAA0319L, AAVR, KIAA1837, PP791 (HUMAN)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[K319L_HUMAN] Systemic lupus erythematosus;Limited cutaneous systemic sclerosis.

Function

[K319L_HUMAN] Possible role in axon guidance through interaction with RTN4R.^[1] [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.^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Adeno-associated virus (AAV) is a leading vector for virus-based gene therapy. The receptor for AAV (AAVR; also named KIAA0319L) was recently identified, and the precise characterization of AAV-AAVR recognition is in immediate demand. Taking advantage of a particle-filtering algorithm, we report here the cryo-electron microscopy structure of the AAV2-AAVR complex at 2.8 A resolution. This structure reveals that of the five Ig-like polycystic kidney disease (PKD) domains in AAVR, PKD2 binds directly to the spike region of the AAV2 capsid adjacent to the icosahedral three-fold axis. Residues in strands B and E, and the BC loop of AAVR PKD2 interact directly with the AAV2 capsid. The interacting residues in the AAV2 capsid are mainly in AAV-featured variable regions. Mutagenesis of the amino acids at the AAV2-AAVR interface reduces binding activity and viral infectivity. Our findings provide insights into the biology of AAV entry with high-resolution details, providing opportunities for the development of new AAV vectors for gene therapy.

Adeno-associated virus 2 bound to its cellular receptor AAVR.,Zhang R, Cao L, Cui M, Sun Z, Hu M, Zhang R, Stuart W, Zhao X, Yang Z, Li X, Sun Y, Li S, Ding W, Lou Z, Rao Z Nat Microbiol. 2019 Feb 11. pii: 10.1038/s41564-018-0356-7. doi:, 10.1038/s41564-018-0356-7. PMID:30742069^[6]

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

References

↑ Poon MW, Tsang WH, Chan SO, Li HM, Ng HK, Waye MM. Dyslexia-associated kiaa0319-like protein interacts with axon guidance receptor nogo receptor 1. Cell Mol Neurobiol. 2011 Jan;31(1):27-35. doi: 10.1007/s10571-010-9549-1. Epub, 2010 Aug 10. PMID:20697954 doi:http://dx.doi.org/10.1007/s10571-010-9549-1
↑ 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
↑ Zhang R, Cao L, Cui M, Sun Z, Hu M, Zhang R, Stuart W, Zhao X, Yang Z, Li X, Sun Y, Li S, Ding W, Lou Z, Rao Z. Adeno-associated virus 2 bound to its cellular receptor AAVR. Nat Microbiol. 2019 Feb 11. pii: 10.1038/s41564-018-0356-7. doi:, 10.1038/s41564-018-0356-7. PMID:30742069 doi:http://dx.doi.org/10.1038/s41564-018-0356-7

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Adeno-Associated Virus 2 in complex with AAVR==
-<StructureSection load='6ihb' size='340' side='right'caption='[[6ihb]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
+<SX load='6ihb' size='340' side='right' viewer='molstar' caption='[[6ihb]], [[Resolution|resolution]] 2.84&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[6ihb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Adeno-associated_virus_2_(isolate_srivastava/1982) Adeno-associated virus 2 (isolate srivastava/1982)] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IHB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IHB FirstGlance]. <br>
@@ Line 23: / Line 23: @@
 <references/>
 __TOC__
-</StructureSection>
+</SX>
 [[Category: Human]]
 [[Category: Large Structures]]

6ihb

From Proteopedia

Revision as of 22:08, 6 March 2020

Adeno-Associated Virus 2 in complex with AAVR

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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