Hofmann Jennifer L, Yang Theodore S, Sunol Alp M, Zia Roseanna N
Department of Chemical Engineering, Stanford University, Stanford, CA, USA.
Department of Mechanical and Aerospace Engineering, University of Missouri, Columbia, MO, USA.
Commun Biol. 2025 Jun 19;8(1):940. doi: 10.1038/s42003-025-08366-4.
Translating ribosomes must wait after each elongation step for a new ternary complex (EF-Tu ⋅ aa-tRNA ⋅ GTP) to arrive, facilitating rapid codon recognition testing. We recently showed that this wait-time rate-limits elongation in Escherichia coli due to competitive combinatoric searching through crowded cytoplasm by thousands of E. coli's 42 unique ternary complexes. Here, we investigate whether ribosomal L12 subunits pool translation molecules to reduce this wait time. We mimic transport and reactions underlying elongation in a physiologically accurate, physically-resolved model of crowded cytoplasm. We find that L12 pre-loading as much as doubles translation rate by reducing diffusive search time. But more L12 is not always better: faster-growing bacteria tend to have fewer L12. We resolve this apparent contradiction by demonstrating tradeoffs between binding and novel sampling as a function of copy number in E. coli. Variable L12 copy numbers may thus have evolved for fast or slow bacterial growth as complementary survival strategies.
在每一步延伸之后，正在翻译的核糖体必须等待新的三元复合物（EF-Tu·氨酰-tRNA·GTP）到来，这有助于快速进行密码子识别测试。我们最近发现，由于大肠杆菌的42种独特三元复合物在拥挤的细胞质中进行竞争性组合搜索，这种等待时间限制了大肠杆菌中的延伸过程。在这里，我们研究核糖体L12亚基是否会聚集翻译分子以减少这种等待时间。我们在一个生理上准确、物理上可解析的拥挤细胞质模型中模拟延伸过程中的转运和反应。我们发现，通过减少扩散搜索时间，L12预加载可使翻译速率提高一倍之多。但更多的L12并不总是更好：生长较快的细菌往往L12较少。我们通过证明在大肠杆菌中结合与新的采样之间的权衡是拷贝数的函数，解决了这一明显的矛盾。因此，可变的L12拷贝数可能作为互补的生存策略，因细菌生长快慢而进化。
