Department of Molecular Microbiology
Rappaport Faculty of Medicine
The Technion - Israel Institute of Technology
Efron St 1
Haifa / ISRAEL
Website Oded Lewinson
”Beyond the Eppendorf tube: the importance of cellular copy numbers and stoichiometries for transmembrane transport”
Recent advances in biophysical and computational approaches provided in-depth insight into the function and structure of membrane transporters. However, since such studies are mostly performed on isolated systems, they do not reveal functional features that are inherent to the cellular context. Specifically, our understanding of the importance of cellular copy numbers, stoichiometries of multi-subunit systems, and subunit interactions remains limited. In this work, we combined proteomics, cellular assays, and mathematical modeling and studied one of the largest protein families of any proteome: ABC transporters.
We observe four orders of magnitude variation in the abundances of the 48 E. coli ABC import systems. We find that cellular copy numbers are finetuned to supply the hierarchy of masses of nutrients that are required for optimal growth. We also observe that the cellular copy numbers of the soluble substrate-binding receptors do not correlate with their substrate binding affinities, but rather with their interaction affinity with their cognate membrane transporters. Further, we find that different systems utilize very different subunit stoichiometries which are correlated with their physiological roles and essential for their function. The results reveal a design principal where cellular abundances, subunit stoichiometries and associations have been shaped to support different cellular requirements and uncover a novel mechanism for high affinity acquisition of rare compounds, one which fully depends on subunit stoichiometry.
Host: Thomas STOCKNER
Contact for questions: Helmut KUBISTA