6nz0

Structural highlights

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]}

References

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ 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
5. ↑ 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