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Adenovirus fibre shaft sequence N-terminally fused to the bacteriophage T4 fibritin foldon trimerisation motif with a long linkerAdenovirus fibre shaft sequence N-terminally fused to the bacteriophage T4 fibritin foldon trimerisation motif with a long linker
Structural highlights
FunctionWAC_BPT4 Chaperone responsible for attachment of long tail fibers to virus particle. Forms the fibrous structure on the neck of the virion called whiskers. During phage assembly, 6 fibritin molecules attach to each virion neck through their N-terminal domains, to form a collar with six fibers ('whiskers').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] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAdenovirus fibres are trimeric proteins that consist of a globular C-terminal domain, a central fibrous shaft and an N-terminal part that attaches to the viral capsid. In the presence of the globular C-terminal domain, which is necessary for correct trimerisation, the shaft segment adopts a triple beta-spiral conformation. We have replaced the head of the fibre by the trimerisation domain of the bacteriophage T4 fibritin, the foldon. Two different fusion constructs were made and crystallised, one with an eight amino acid residue linker and one with a linker of only two residues. X-ray crystallographic studies of both fusion proteins shows that residues 319-391 of the adenovirus type 2 fibre shaft fold into a triple beta-spiral fold indistinguishable from the native structure, although this is now resolved at a higher resolution of 1.9 A. The foldon residues 458-483 also adopt their natural structure. The intervening linkers are not well ordered in the crystal structures. This work shows that the shaft sequences retain their capacity to fold into their native beta-spiral fibrous fold when fused to a foreign C-terminal trimerisation motif. It provides a structural basis to artificially trimerise longer adenovirus shaft segments and segments from other trimeric beta-structured fibre proteins. Such artificial fibrous constructs, amenable to crystallisation and solution studies, can offer tractable model systems for the study of beta-fibrous structure. They can also prove useful for gene therapy and fibre engineering applications. Adenovirus fibre shaft sequences fold into the native triple beta-spiral fold when N-terminally fused to the bacteriophage T4 fibritin foldon trimerisation motif.,Papanikolopoulou K, Teixeira S, Belrhali H, Forsyth VT, Mitraki A, van Raaij MJ J Mol Biol. 2004 Sep 3;342(1):219-27. PMID:15313619[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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