正文 · AI 翻译
IT Home reported on November 5 that Anthropic announced today that its biology research team, with the help of Claude, had determined for the first time the three-dimensional structure of a vault particle associated with prokaryotes (a vesicle-like protein complex).
The study found that a protein from a bacteriophage can assemble into a complete vault particle made up of 96 identical proteins, with a total molecular mass of about 9.5 megadaltons (MDa) and an enclosed volume about 25% larger than that of the corresponding structure in human cells.
IT Home notes: Vault particles are among the largest ribonucleoprotein particles in cells. Human cells contain about 10,000 of them. A typical particle measures about 67 nanometers long and 40 nanometers wide. Scientists first discovered them in 1986, but their biological function has remained unknown for about 40 years.
The research team searched about 15 billion predicted protein sequences for homologs of major vault protein (MVP), found candidate sequences in 29 bacterial phyla and 4 archaeal phyla, and selected 44 proteins for laboratory testing.
Experiments showed that 7 of the proteins expressed in E. coli assembled into vault-like particles. Cryo-electron microscopy confirmed complete, closed structures for 4 candidates: 2 from bacteria and 2 from bacteriophages.
The research team focused on the bacteriophage-derived L05 protein, resolving its structure to 3.2 angstroms. The L05 vault consists of 96 protein chains, each with 7 wall repeats, compared with 9 in human MVP. The L05 particle is 54.5 nanometers long and 47.5 nanometers wide, has a more spherical shape, and has an internal volume about 25% larger than a human vault.
The team then inserted additional wall repeats into L05 to produce the L05+2 and L05+4 variants. The cryo-electron microscopy structure of L05+2 showed increases in both particle length and width, with internal volume rising by a further roughly 20% to a total volume about 50% larger than that of a human vault. This indicates that the number of wall repeats can be used to engineer vault size.
Structural analysis also found a stretch of unassigned density on the inner wall of L05. Computational searches suggested that coenzyme A or a derivative was the most likely ligand. The inner wall of human vaults likewise binds nucleotide molecules such as NAD+, suggesting that the inner surface of the vault cavity may be a region that binds small molecules and partner proteins.
Claude participated in the protein search, DNA sequence design, purification workflow optimization, and cryo-electron microscopy data processing in this study. Traditional vault purification methods take about 3 days; a size-exclusion chromatography procedure developed by the team cut that time to about 90 minutes. The first complete structural model was generated within 34 hours, compared with the several weeks expected for conventional analysis.
The research process also exposed AI's limitations. In one experimental protocol, an additive suggested by Claude interfered with DNA delivery, delaying the research by 2 weeks. During cryo-electron microscopy data processing, Claude skipped standard steps and generated an inaccurate structural map; the team corrected the problem through closer supervision.
Although the structure has been resolved, the vault particle's actual function in living cells remains undetermined. The discovery of prokaryotic vaults provides a more manageable experimental system for studying assembly mechanisms, as well as a protein scaffold whose size can be adjusted for cargo encapsulation. Structural data for L05 and its engineered variants have been deposited in the Protein Data Bank.
Paper URL:
https://www-cdn.anthropic.com/76e55fbe85697afbaae16b839498dc00797dec30.pdf
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