title: The morphogenic linker peptide of HBV capsid protein forms a mobile array on the interior surface.
abstract: Many capsid proteins have peptides that influence their assembly. In hepatitis B virus capsid protein, the peptide STLPETTVV, linking the shell-forming 'core' domain and the nucleic acid-binding 'protamine' domain, has such a role. We have studied its morphogenic properties by permuting its sequence, substituting it with an extraneous peptide, deleting it to directly fuse the core and protamine domains and assembling core domain dimers with added linker peptides. The peptide was found to be necessary for the assembly of protamine domain-containing capsids, although its size-determining effect tolerates some modifications. Although largely invisible in a capsid crystal structure, we could visualize linker peptides by cryo-EM difference imaging: they emerge on the inner surface and extend from the capsid protein dimer interface towards the adjacent symmetry axis. A closely sequence-similar peptide in cellobiose dehydrogenase, which has an extended conformation, offers a plausible prototype. We propose that linker peptides are attached to the capsid inner surface as hinged struts, forming a mobile array, an arrangement with implications for morphogenesis and the management of encapsidated nucleic acid.
authors.affiliation: Protein Expression Laboratory, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Building 50, Room 1517, 50 South drive MSC 8025, National Institutes of Health, Bethesda, MD 20892-8025, USA.
authors.forename: Norman R
authors.initials: NR
authors.lastname: Watts
authors.forename: James F
authors.initials: JF
authors.lastname: Conway
authors.forename: Naiqian
authors.initials: N
authors.lastname: Cheng
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Stahl
authors.forename: David M
authors.initials: DM
authors.lastname: Belnap
authors.forename: Alasdair C
authors.initials: AC
authors.lastname: Steven
authors.forename: Paul T
authors.initials: PT
authors.lastname: Wingfield
mesh_terms: D019943:Amino Acid Substitution; D002213:Capsid / Q000648:ultrastructure*; D002237:Carbohydrate Dehydrogenases / Q000737:chemistry; D002850:Chromatography, Gel; D002942:Circular Dichroism; D020285:Cryoelectron Microscopy; D003460:Crystallization; D004926:Escherichia coli; D006512:Hepatitis B Core Antigens / Q000737:chemistry* / Q000648:ultrastructure; D006513:Hepatitis B e Antigens / Q000737:chemistry* / Q000648:ultrastructure; D006515:Hepatitis B virus / Q000648:ultrastructure*; D007091:Image Processing, Computer-Assisted; D008958:Models, Molecular; D009024:Morphogenesis; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000648:ultrastructure; D013329:Structure-Activity Relationship; D013382:Subtraction Technique
chemical_list: D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D002237:Carbohydrate Dehydrogenases; C019859:cellobiose-quinone oxidoreductase