The synthesis of eukaryotic glycans - branched sugar oligomers attached to cell-surface proteins and lipids - is organised like a factory assembly line. Specific enzymes within successive compartments of the Golgi apparatus determine where new monomer building blocks are linked to the growing oligomer. These enzymes act promiscuously and stochastically, causing microheterogeneity (molecule-to-molecule variability) in the final oligomer products. However, this variability is tightly controlled: a given eukaryotic protein type is typically associated with a narrow, specific glycan oligomer profile. Here we use ideas from the mathematical theory of self-assembly to enumerate the enzymatic causes of oligomer variability, and show how to eliminate each cause. We rigorously demonstrate that cells can specifically synthesize a larger repertoire of glycan oligomers by partitioning promiscuous enzymes across multiple Golgi compartments. This places limits on biomolecular assembly: glycan microheterogeneity becomes unavoidable when the number of compartments is limited, or enzymes are excessively promiscuous.
- Mukund Thattai
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Patricia Bassereau, Institut Curie, France
- Received: June 21, 2019
- Accepted: June 28, 2020
- Accepted Manuscript published: June 29, 2020 (version 1)
© 2020, Jaiman & Thattai
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.