7OD7

Hepatitis B core protein + SLLGRM

Summary for 7OD7

• Entry DOI: 10.2210/pdb7od7/pdb
• Related: 7OCO 7OCW 7OD4 7OD6
• EMDB information: 12810 12815 12819 12820 12821
• Descriptor: Capsid protein, SLLRGM (2 entities in total)
• Functional Keywords: hepatitis b core protein, virus like particle, inhibitory peptide
• Biological source: Hepatitis B virus genotype D subtype ayw (isolate France/Tiollais/1979) (HBV-D); More
• Total number of polymer chains: 5
• Total formula weight: 85772.35

Authors

Bottcher, B.,Makbul, C. (deposition date: 2021-04-28, release date: 2021-05-26, Last modification date: 2024-07-10)

Primary citation

Makbul, C.,Khayenko, V.,Maric, H.M.,Bottcher, B.
Conformational Plasticity of Hepatitis B Core Protein Spikes Promotes Peptide Binding Independent of the Secretion Phenotype.
Microorganisms, 9:-, 2021

PubMed Abstract: Hepatitis B virus is a major human pathogen, which forms enveloped virus particles. During viral maturation, membrane-bound hepatitis B surface proteins package hepatitis B core protein capsids. This process is intercepted by certain peptides with an "LLGRMKG" motif that binds to the capsids at the tips of dimeric spikes. With microcalorimetry, electron cryo microscopy and peptide microarray-based screens, we have characterized the structural and thermodynamic properties of peptide binding to hepatitis B core protein capsids with different secretion phenotypes. The peptide "GSLLGRMKGA" binds weakly to hepatitis B core protein capsids and mutant capsids with a premature (F97L) or low-secretion phenotype (L60V and P5T). With electron cryo microscopy, we provide novel structures for L60V and P5T and demonstrate that binding occurs at the tips of the spikes at the dimer interface, splaying the helices apart independent of the secretion phenotype. Peptide array screening identifies "SLLGRM" as the core binding motif. This shortened motif binds only to one of the two spikes in the asymmetric unit of the capsid and induces a much smaller conformational change. Altogether, these comprehensive studies suggest that the tips of the spikes act as an autonomous binding platform that is unaffected by mutations that affect secretion phenotypes.

PubMed: 33946808
DOI: 10.3390/microorganisms9050956

Experimental method

ELECTRON MICROSCOPY (2.8 Å)