1o6e | pdb_00001o6e
Epstein-Barr virus protease
Structural highlights
Function[SCAF_EBVB9] Capsid scaffolding protein acts as a scaffold protein by binding major capsid protein BcLF1 in the cytoplasm, inducing the nuclear localization of both proteins. Multimerizes in the nucleus such as BcLF1 forms the icosahedral T=16 capsid. Autocatalytic cleavage releases the assembly protein, and subsequently abolishes interaction with major capsid protein BcLF1. Cleavages products are evicted from the capsid before or during DNA packaging.[1] Assemblin is a protease essential for virion assembly in the nucleus. Catalyzes the cleavage of the assembly protein after complete capsid formation. Assemblin and cleavages products are evicted from the capsid before or during DNA packaging.[2] Assembly protein plays a major role in capsid assembly. Acts as a scaffold protein by binding major capsid protein BcLF1. Multimerizes in the nucleus such as BcLF1 forms the icosahedral T=16 capsid. Cleaved by assemblin after capsid completion. The cleavages products are evicted from the capsid before or during DNA packaging.[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 PubMedEpstein-Barr virus (EBV) belongs to the gamma-herpesvirinae subfamily of the Herpesviridae. The protease domain of the assemblin protein of herpesviruses forms a monomer-dimer equilibrium in solution. The protease domain of EBV was expressed in Escherichia coli and its structure was solved by X-ray crystallography to 2.3A resolution after inhibition with diisopropyl-fluorophosphate (DFP). The overall structure confirms the conservation of the homodimer and its structure throughout the alpha, beta, and gamma-herpesvirinae. The substrate recognition could be modelled using information from the DFP binding, from a crystal contact, suggesting that the substrate forms an antiparallel beta-strand extending strand beta5, and from the comparison with the structure of a peptidomimetic inhibitor bound to cytomegalovirus protease. The long insert between beta-strands 1 and 2, which was disordered in the KSHV protease structure, was found to be ordered in the EBV protease and shows the same conformation as observed for proteases in the alpha and beta-herpesvirus families. In contrast to previous structures, the long loop located between beta-strands 5 and 6 is partially ordered, probably due to DFP inhibition and a crystal contact. It also contributes to substrate recognition. The protease shows a specific recognition of its own C terminus in a binding pocket involving residue Phe210 of the other monomer interacting across the dimer interface. This suggests conformational changes of the protease domain after its release from the assemblin precursor followed by burial of the new C terminus and a possible effect onto the monomer-dimer equilibrium. The importance of the processed C terminus was confirmed using a mutant protease carrying a C-terminal extension and a mutated release site, which shows different solution properties and a strongly reduced enzymatic activity. The crystal structure of the Epstein-Barr virus protease shows rearrangement of the processed C terminus.,Buisson M, Hernandez JF, Lascoux D, Schoehn G, Forest E, Arlaud G, Seigneurin JM, Ruigrok RW, Burmeister WP J Mol Biol. 2002 Nov 15;324(1):89-103. PMID:12421561[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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