6nz0

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(Difference between revisions)

Revision as of 11:49, 18 December 2019

Cryo-EM structure of AAV-2 in complex with AAVR PKD domains 1 and 2

Structural highlights

6nz0 is a 2 chain structure with sequence from Aav-2 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	KIAA0319L, AAVR, KIAA1837, PP791 (HUMAN), VP1 (AAV-2)
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) vectors are preeminent in emerging clinical gene therapies. Generalizing beyond the most tractable genetic diseases will require modulation of cell specificity and immune neutralization. Interactions of AAV with its cellular receptor, AAVR, are key to understanding cell-entry and trafficking with the rigor needed to engineer tissue-specific vectors. Cryo-electron tomography shows ordered binding of part of the flexible receptor to the viral surface, with distal domains in multiple conformations. Regions of the virus and receptor in close physical proximity can be identified by cross-linking/mass spectrometry. Cryo-electron microscopy with a two-domain receptor fragment reveals the interactions at 2.4 A resolution. AAVR binds between AAV's spikes on a plateau that is conserved, except in one clade whose structure is AAVR-incompatible. AAVR's footprint overlaps the epitopes of several neutralizing antibodies, prompting a re-evaluation of neutralization mechanisms. The structure provides a roadmap for experimental probing and manipulation of viral-receptor interactions.

Structure of the gene therapy vector, adeno-associated virus with its cell receptor, AAVR.,Meyer NL, Hu G, Davulcu O, Xie Q, Noble AJ, Yoshioka C, Gingerich DS, Trzynka A, David L, Stagg SM, Chapman MS Elife. 2019 May 22;8. pii: 44707. doi: 10.7554/eLife.44707. PMID:31115336^[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
↑ Meyer NL, Hu G, Davulcu O, Xie Q, Noble AJ, Yoshioka C, Gingerich DS, Trzynka A, David L, Stagg SM, Chapman MS. Structure of the gene therapy vector, adeno-associated virus with its cell receptor, AAVR. Elife. 2019 May 22;8. pii: 44707. doi: 10.7554/eLife.44707. PMID:31115336 doi:http://dx.doi.org/10.7554/eLife.44707

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/6nz0"

@@ Line 3: / Line 3: @@
 <StructureSection load='6nz0' size='340' side='right'caption='[[6nz0]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6nz0]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NZ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NZ0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6nz0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Aav-2 Aav-2] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NZ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NZ0 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KIAA0319L, AAVR, KIAA1837, PP791 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), VP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=648242 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=6nz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nz0 OCA], [http://pdbe.org/6nz0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nz0 RCSB], [http://www.ebi.ac.uk/pdbsum/6nz0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nz0 ProSAT]</span></td></tr>
 </table>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Aav-2]]
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Chapman, M S]]

6nz0

From Proteopedia

Revision as of 11:49, 18 December 2019

Cryo-EM structure of AAV-2 in complex with AAVR PKD domains 1 and 2

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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