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-Structure paper
タイトル | Binding of a Pocket Factor to Hepatitis B Virus Capsids Changes the Rotamer Conformation of Phenylalanine 97. |
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ジャーナル・号・ページ | Viruses, Vol. 13, Issue 11, Year 2021 |
掲載日 | 2021年10月20日 |
著者 | Cihan Makbul / Christian Kraft / Matthias Grießmann / Tim Rasmussen / Kilian Katzenberger / Melina Lappe / Paul Pfarr / Cato Stoffer / Mara Stöhr / Anna-Maria Wandinger / Bettina Böttcher / |
PubMed 要旨 | (1) Background: During maturation of the Hepatitis B virus, a viral polymerase inside the capsid transcribes a pre-genomic RNA into a partly double stranded DNA-genome. This is followed by ...(1) Background: During maturation of the Hepatitis B virus, a viral polymerase inside the capsid transcribes a pre-genomic RNA into a partly double stranded DNA-genome. This is followed by envelopment with surface proteins inserted into a membrane. Envelopment is hypothetically regulated by a structural signal that reports the maturation state of the genome. NMR data suggest that such a signal can be mimicked by the binding of the detergent Triton X 100 to hydrophobic pockets in the capsid spikes. (2) Methods: We have used electron cryo-microscopy and image processing to elucidate the structural changes that are concomitant with the binding of Triton X 100. (3) Results: Our maps show that Triton X 100 binds with its hydrophobic head group inside the pocket. The hydrophilic tail delineates the outside of the spike and is coordinated via Lys-96. The binding of Triton X 100 changes the rotamer conformation of Phe-97 in helix 4, which enables a π-stacking interaction with Trp-62 in helix 3. Similar changes occur in mutants with low secretion phenotypes (P5T and L60V) and in a mutant with a pre-mature secretion phenotype (F97L). (4) Conclusion: Binding of Triton X 100 is unlikely to mimic structural maturation because mutants with different secretion phenotypes show similar structural responses. |
リンク | Viruses / PubMed:34834922 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.8 - 3.2 Å |
構造データ | EMDB-13726, PDB-7pz9: EMDB-13728, PDB-7pzi: EMDB-13731, PDB-7pzk: EMDB-13732, PDB-7pzl: EMDB-13733, PDB-7pzm: EMDB-13734, PDB-7pzn: |
化合物 | ChemComp-TRT: |
由来 |
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キーワード | VIRUS LIKE PARTICLE / Icosahedral capsid like particle with T=4 / VIRAL PROTEIN / Pocket binding factor mimic Triton X-100 / premature secretion phenotype / hepatitis B virus / HBc-WT in complex with Triton X-100 / HBc-L60V (low secretion phenotype) in complex with Triton X-100 / HBc-P5T (low secretion phenotype) in complex with Triton X-100 / wt HBc capsid / Triton X-100 / inhibitory peptide SLLGRM / Cryo-EM |