Combination of deep XLMS with deep learning reveals an ordered rearrangement and assembly of a major protein component of the vaccinia virion.
Combination of deep XLMS with deep learning reveals an ordered rearrangement and assembly of a major protein component of the vaccinia virion.
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痘苗病毒是典型的天花病毒和天花/猴痘疫苗，已被证明是结构生物学的一个具有挑战性的实体，无视许多导致其他病毒的分子和原子模型的方法。通过深度学习和交联质谱学的结合，我们建立了痘苗病毒结构成分P4A蛋白的原子水平模型和完整的加工/组装途径。在该途径中，P4A的C-末端P4A-3片段的蛋白水解性分离在N-末端P4A-1片段内触发了大量的构象旋转，该构象旋转通过二硫键锁定而变得固定，同时去除了加工中间体P4A-1+2的空间位阻。这些事件触发了P4A-2的蛋白质水解性分离，允许P4A-1组装成包围新生病毒核心的六角形晶格。理解痘病毒生物学的一个突出问题是成熟病毒粒子的分子结构。通过深度学习和化学交联质谱学相结合的方法，我们研究了痘病毒核心成分P4A的结构和组装途径。
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 assembly of P4a-1 into a hexagonal lattice that encloses the nascent virion core. An outstanding problem in the understanding of poxvirus biology is the molecular structure of the mature virion. Via deep learning methods combined with chemical cross-linking mass spectrometry, we have addressed the structure and assembly pathway of P4a, a key poxvirus virion core component.
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影响因子：
3.7
作者：
Jesus, Desyree Murta;Moussatche, Nissin;McFadden, Baron B. D.;Nielsen, Casey Paulasue;D'Costa, Susan M.;Condit, Richard C.
通讯作者：
Condit, Richard C.
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作者：
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影响因子：
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