Combination of deep XLMS with deep learning reveals an ordered rearrangement and assembly of a major protein component of the vaccinia virion.

ABSTRACT: Vaccinia virus, the prototypical poxvirus and smallpox/monkeypox vaccine, has proven a challenging entity for structural biology, defying many of the approaches leading to molecular and atomic models for other viruses. Via a combination of deep learning and cross-linking mass spectrometry, we have developed an atomic-level model and an integrated processing/assembly pathway for a structural component of the vaccinia virion, protein P4a. Within the pathway, proteolytic separation of the C-terminal P4a-3 segment of P4a triggers a massive conformational rotation within the N-terminal P4a-1 segment that becomes fixed by disulfide-locking while removing a steric block to trimerization of the processing intermediate P4a-1+2. These events trigger the proteolytic separation of P4a-2, allowing the

SUBMITTER: Mirzakhanyan Y 

PROVIDER: S-EPMC10653903 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature