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| Towards a complete atomic model of the adenovirus capsid | |
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The adenovirus penton, composed of a non-covalent complex of the
pentameric penton base and trimeric fibre proteins, is a major component
of the adenovirus capsid and it contains all necessary components for
viral attachment and internalisation. The human adenovirus 2 penton
base has been crystallised in a dodecahedral form (12 pentons forming an
icosahedral particle). The structure was determined at 3.3Å resolution
using a low resolution cryo-EM model for molecular replacement followed
by 60-fold non-crystallographic symmetry averaging and phase extension.
The penton base monomer has a two-domain topology, a basal antiparallel
beta strand jellyroll domain and a distal insertion domain formed by two
long insertions into the jellyroll motif. This general topology is
similar to that of the adenovirus hexon and several other viral capsid
proteins. The RGD motif, required for cell internalisation through
interactions with integrins, is found on a long flexible surface loop.
The penton base was co-crystallised with a 20 residues peptide
corresponding to the N-terminus of the fibre polypeptide. The structure
of the N-terminal fibre peptide bound to the penton base shows five
equivalent sites of interaction, although only three would normally be
occupied by the trimeric fibre. The universally conserved FNPVYPY motif
of the fibre binds to conserved regions at the interface of adjacent
penton base monomers and results in a localised structural
re-arrangement in the insertion domain of the base. The penton base is
the last major capsid protein of adenovirus to have its structure
determined and allows a complete quasi-atomic model of the adenovirus
capsid to be constructed using a new 12Å resolution cryo-EM map of the
entire virus.
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