| Structural highlights
4ar2 is a 2 chain structure with sequence from Ade03. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| Related: | 1qhv, 1qiu, 1v1h, 1v1i, 2c9f, 4aqq |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SPIKE_ADE02] Forms spikes that protrude from each vertex of the icosahedral capsid. Interacts with host coxsackievirus and adenovirus receptor CXADR located at the cell tight junctions to provide virion initial attachment to target cell. The fiber protein binds to CXADR with a higher affinity than CXADR binds to itself, thereby blocking the cell-cell adhesion function of CXADR dimers and leading to local disruption of the tight junction. Fiber protein present on neo-synthesized particles may thus disrupt the junctional integrity in order to facilitate further neighboring cells infection. Fiber proteins are shed during virus entry, when virus is still at the cell surface. Fiber shedding is dependent on viral CXADR drifting motion and subsequent binding to immobile integrins. Heparan sulfate might also play a role in virus binding.[1] [2] [3] [4]
Publication Abstract from PubMed
During the viral life cycle adenoviruses produce excess capsid proteins. Human adenovirus serotype 3 (Ad3) synthesizes predominantly an excess of free pentons, the complexes of pentameric penton base and trimeric fiber proteins, which are responsible for virus penetration. In infected cells Ad3 pentons spontaneously assemble into dodecahedral virus-like nano-particles containing twelve pentons. They also form in insect cells during expression in the baculovirus system. Similarly, in the absence of fiber protein dodecahedric particles built of 12 penton base pentamers can be produced. Both kinds of dodecahedra show remarkable efficiency of intracellular penetration and can be engineered to deliver several millions of foreign cargo molecules to a single target cell. For this reason, they are of great interest as a delivery vector. In order to successfully manipulate this potential vector for drug and/or gene delivery, an understanding of the molecular basis of vector assembly and integrity is critical. Crystallographic data in conjunction with site-directed mutagenesis and biochemical analysis provide a model for the molecular determinants of dodecamer particle assembly and the requirements for stability. The 3.8 A crystal structure of Ad3 penton base dodecamer (Dd) shows that the dodecahedric structure is stabilized by strand-swapping between neighboring penton base molecules. Such N-terminal strand-swapping does not occur for Dd of Ad2, a serotype which does not form Dd under physiological conditions. This unique stabilization of the Ad3 dodecamer is controlled by residues 59-61 located at the site of strand switching, the residues involved in putative salt bridges between pentamers and by the disordered N-terminus (residues 1-47), as confirmed by site directed mutagenesis and biochemical analysis of mutant and wild type protein. We also provide evidence that the distal N-terminal residues are externally exposed and available for attaching cargo.
The structural basis for the integrity of adenovirus ad3 dodecahedron.,Szolajska E, Burmeister WP, Zochowska M, Nerlo B, Andreev I, Schoehn G, Andrieu JP, Fender P, Naskalska A, Zubieta C, Cusack S, Chroboczek J PLoS One. 2012;7(9):e46075. doi: 10.1371/journal.pone.0046075. Epub 2012 Sep 25. PMID:23049939[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Dechecchi MC, Tamanini A, Bonizzato A, Cabrini G. Heparan sulfate glycosaminoglycans are involved in adenovirus type 5 and 2-host cell interactions. Virology. 2000 Mar 15;268(2):382-90. PMID:10704346 doi:http://dx.doi.org/10.1006/viro.1999.0171
- ↑ Walters RW, Freimuth P, Moninger TO, Ganske I, Zabner J, Welsh MJ. Adenovirus fiber disrupts CAR-mediated intercellular adhesion allowing virus escape. Cell. 2002 Sep 20;110(6):789-99. PMID:12297051
- ↑ Burckhardt CJ, Suomalainen M, Schoenenberger P, Boucke K, Hemmi S, Greber UF. Drifting motions of the adenovirus receptor CAR and immobile integrins initiate virus uncoating and membrane lytic protein exposure. Cell Host Microbe. 2011 Aug 18;10(2):105-17. doi: 10.1016/j.chom.2011.07.006. PMID:21843868 doi:http://dx.doi.org/10.1016/j.chom.2011.07.006
- ↑ Wang K, Huang S, Kapoor-Munshi A, Nemerow G. Adenovirus internalization and infection require dynamin. J Virol. 1998 Apr;72(4):3455-8. PMID:9525681
- ↑ Szolajska E, Burmeister WP, Zochowska M, Nerlo B, Andreev I, Schoehn G, Andrieu JP, Fender P, Naskalska A, Zubieta C, Cusack S, Chroboczek J. The structural basis for the integrity of adenovirus ad3 dodecahedron. PLoS One. 2012;7(9):e46075. doi: 10.1371/journal.pone.0046075. Epub 2012 Sep 25. PMID:23049939 doi:http://dx.doi.org/10.1371/journal.pone.0046075
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