TY  - JOUR
A1  - Makbul, Cihan
A1  - Kraft, Christian
A1  - Grießmann, Matthias
A1  - Rasmussen, Tim
A1  - Katzenberger, Kilian
A1  - Lappe, Melina
A1  - Pfarr, Paul
A1  - Stoffer, Cato
A1  - Stöhr, Mara
A1  - Wandinger, Anna-Maria
A1  - Böttcher, Bettina
T1  - Binding of a pocket factor to Hepatitis B virus capsids changes the rotamer conformation of Phenylalanine 97
JF  - Viruses
N2  - (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.
KW  - Hepatitis B Virus
KW  - pocket factor
KW  - Triton X 100
KW  - envelopment
KW  - maturation signal
KW  - single strand blocking
KW  - electron cryo-microscopy
KW  - isothermal titration calorimetry
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248565
SN  - 1999-4915
VL  - 13
IS  - 11
ER  -