2fun

alternative p35-caspase-8 complexalternative p35-caspase-8 complex

Structural highlights

2fun is a 4 chain structure with sequence from Autographa californica nucleopolyhedrovirus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

P35_NPVAC Functions as an inhibitor of the host RNA interference antiviral response. Inhibits the insect host cell apoptotic response initiated by the viral infection. Blocks as well the activity of members of the caspase family of proteases. Required for late and very late gene expression.^[1] ^[2] ^[3]

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 PubMed

Wide-spectrum caspase inhibition by the baculoviral p35 protein was previously shown to be a consequence of covalent inhibition in which a thioester bond is stably formed between the cleavage residue Asp87 of p35 and the active site Cys360' of caspase-8. Here we show that the N-terminal fragment of cleaved p35 (p35-N) is a circular peptide when dissociated from the caspase. Biochemical and crystallographic data suggest that p35-N circularization results from the trapping of a native chemical ligation intermediate in the p35/caspase complex, in which the N-terminal Cys2 of p35 attacks the Asp87-Cys360' thioester to form an equilibrium between Asp87-Cys2 and Asp87-Cys360'. This provides a crucial covalent interaction for keeping the N terminus of p35 bound in the caspase active site, which explains the absolute requirement of Cys2 for caspase inhibition. Participation of native chemical ligation in caspase inhibition by p35 illustrates an unusual mechanism of protease inhibition.

Native chemical ligation in covalent caspase inhibition by p35.,Lu M, Min T, Eliezer D, Wu H Chem Biol. 2006 Feb;13(2):117-22. PMID:16492559^[4]

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

References

↑ da Silveira EB, Cordeiro BA, Ribeiro BM, Báo SN. In vivo apoptosis induction and reduction of infectivity by an Autographa californica multiple nucleopolyhedrovirus p35(-) recombinant in hemocytes from the velvet bean caterpillar Anticarsia gemmatalis (Hübner) (Lepidoptera: Noctuidae). Res Microbiol. 2005 Dec;156(10):1014-25. PMID:16081248 doi:10.1016/j.resmic.2005.06.001
↑ Clem RJ, Fechheimer M, Miller LK. Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science. 1991 Nov 29;254(5036):1388-90. PMID:1962198 doi:10.1126/science.1962198
↑ Mehrabadi M, Hussain M, Matindoost L, Asgari S. The Baculovirus Antiapoptotic p35 Protein Functions as an Inhibitor of the Host RNA Interference Antiviral Response. J Virol. 2015 Aug;89(16):8182-92. PMID:26018163 doi:10.1128/JVI.00802-15
↑ Lu M, Min T, Eliezer D, Wu H. Native chemical ligation in covalent caspase inhibition by p35. Chem Biol. 2006 Feb;13(2):117-22. PMID:16492559 doi:10.1016/j.chembiol.2005.12.007

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OCA

[1] Silveira EB, Cordeiro BA, Ribeiro BM, Báo SN. In vivo apoptosis induction and reduction of infectivity by an Autographa californica multiple nucleopolyhedrovirus p35(-) recombinant in hemocytes from the velvet bean caterpillar Anticarsia gemmatalis (Hübner) (Lepidoptera: Noctuidae). Res Microbiol. 2005 Dec;156(10):1014-25. PMID:16081248 doi:10.1016/j.resmic.2005.06.001

[2] Clem RJ, Fechheimer M, Miller LK. Prevention of apoptosis by a baculovirus gene during infection of insect cells. Science. 1991 Nov 29;254(5036):1388-90. PMID:1962198 doi:10.1126/science.1962198

[3] Mehrabadi M, Hussain M, Matindoost L, Asgari S. The Baculovirus Antiapoptotic p35 Protein Functions as an Inhibitor of the Host RNA Interference Antiviral Response. J Virol. 2015 Aug;89(16):8182-92. PMID:26018163 doi:10.1128/JVI.00802-15

[4] Lu M, Min T, Eliezer D, Wu H. Native chemical ligation in covalent caspase inhibition by p35. Chem Biol. 2006 Feb;13(2):117-22. PMID:16492559 doi:10.1016/j.chembiol.2005.12.007

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