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J Virol. 2019 Apr 17;93(9). pii: e00007-19. doi: 10.1128/JVI.00007-19. Print 2019 May 1.

Conservation and Divergence of the I-Domain Inserted into the Ubiquitous HK97 Coat Protein Fold in P22-Like Bacteriophages.

Author information

1
Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut, USA.
2
Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut, USA andrei@uconn.edu carolyn.teschke@uconn.edu.
3
Department of Chemistry, University of Connecticut, Storrs, Connecticut, USA.

Abstract

Despite very low sequence homology, the major capsid proteins of double-stranded DNA (dsDNA) bacteriophages, some archaeal viruses, and the herpesviruses share a structural motif, the HK97 fold. Bacteriophage P22, a paradigm for this class of viruses, belongs to a phage gene cluster that contains three homology groups: P22-like, CUS-3-like, and Sf6-like. The coat protein of each phage has an inserted domain (I-domain) that is more conserved than the rest of the coat protein. In P22, loops in the I-domain are critical for stabilizing intra- and intersubunit contacts that guide proper capsid assembly. The nuclear magnetic resonance (NMR) structures of the P22, CUS-3, and Sf6 I-domains reveal that they are all six-stranded, anti-parallel β-barrels. Nevertheless, significant structural differences occur in loops connecting the β-strands, in surface electrostatics used to dock the I-domains with their respective coat protein core partners, and in sequence motifs displayed on the capsid surfaces. Our data highlight the structural diversity of I-domains that could lead to variations in capsid assembly mechanisms and capsid surfaces adapted for specific phage functions.IMPORTANCE Comparative studies of protein structures often provide insights into their evolution. The HK97 fold is a structural motif used to form the coat protein shells that encapsidate the genomes of many dsDNA phages and viruses. The structure and function of coat proteins based on the HK97 fold are often embellished by the incorporation of I-domains. In the present work we compare I-domains from three phages representative of highly divergent P22-like homology groups. While the three I-domains share a six-stranded β-barrel skeleton, there are differences (i) in structure elements at the periphery of the conserved fold, (ii) in the locations of disordered loops important in capsid assembly and conformational transitions, (iii) in surfaces charges, and (iv) in sequence motifs that are potential ligand-binding sites. These structural modifications on the rudimentary I-domain fold suggest that considerable structural adaptability was needed to fulfill the versatile range of functional requirements for distinct phages.

KEYWORDS:

dsDNA viruses; nuclear magnetic resonance; protein evolution; protein structure

PMID:
30787158
PMCID:
PMC6475800
[Available on 2019-10-17]
DOI:
10.1128/JVI.00007-19

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