6vzp | pdb_00006vzp
HBV wild type capsid
Structural highlights
Function[CAPSD_HBVD1] Self assembles to form an icosahedral capsid. Most capsid appear to be large particles with a icosahedral symmetry of T=4 and consist of 240 copies of capsid protein, though a fraction forms smaller T=3 particles consisting of 180 capsid proteins. Entering capsid are transported along microtubules to the nucleus. Phosphorylation of the capsid is thought to induce exposure of nuclear localization signal in the C-terminal portion of the capsid protein that allows binding to the nuclear pore complex via the importin (karyopherin-) alpha and beta. Capsids are imported in intact form through the nuclear pore into the nuclear basket, where it probably binds NUP153. Only capsids that contain the mature viral genome can release the viral DNA and capsid protein into the nucleoplasm. Immature capsids get stucked in the basket. Capsids encapsulate the pre-genomic RNA and the P protein. Pre-genomic RNA is reverse transcribed into DNA while the capsid is still in the cytoplasm. The capsid can then either be directed to the nucleus, providing more genome for transcription, or bud through the endoplasmic reticulum to provide new virions (By similarity).[1] Encapsidates hepatitis delta genome (By similarity).[2] Publication Abstract from PubMedDuring the hepatitis B virus lifecycle, 120 copies of homodimeric capsid protein assemble around a copy of reverse transcriptase and viral RNA and go on to produce an infectious virion. Assembly needs to be tightly regulated by protein conformational change to ensure symmetry, fidelity and reproducibility. Here we show that structures at the intradimer interface regulate conformational changes at the distal interdimer interface and so regulate assembly. A pair of interacting charged residues, D78 from each monomer, conspicuously located at the top of a four-helix bundle that forms the intradimer interface, were mutated to serine to disrupt communication between the two monomers. The mutation slowed assembly and destabilized dimer to thermal and chemical denaturation. Mutant dimers showed evidence of transient partial unfolding based on appearance of new proteolytically-sensitive sites. Though mutant dimer was less stable, the resulting capsids were as stable as wildtype, based on assembly and thermal denaturation studies. Cryo-EM image reconstructions of capsid indicated that the subunits adopted an "open" state more usually associated with free dimer and that the spike tips were either disordered or highly flexible. Molecular dynamics simulations provide mechanistic explanations for these results, suggesting that D78 stabilizes helix 4a, which forms part of the intradimer interface, by capping its N-terminus and hydrogen-bonding to nearby residues, whereas the D78S mutation disrupts these interactions, leading to partial unwinding of helix 4a. This in turn weakens the connection from helix 4 and the intradimer interface to helix 5, which forms the interdimer interface. . The integrity of the intradimer interface of the Hepatitis B Virus capsid protein dimer regulates capsid self-assembly.,Zhao Z, Wang JC, Segura CP, Hadden-Perilla JA, Zlotnick A ACS Chem Biol. 2020 May 27. doi: 10.1021/acschembio.0c00277. PMID:32459465[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||
