Figure 1.
Models defined by number of binding sites.
Schematic of the 4 models defined by the number of binding sites.
Figure 2.
Schematic of the processes in the ER and their spatial location.
Protein translocation occurs at the ER membrane, while the other processes can occur in the ER lumen. Processes include: (a) translocation; (b) folding/unfolding/misfolding; (c) aggregation; (d) disaggregation; (e) sequestration. Species are represented as follows: nascent protein (N); folded protein (F); unfolded protein (U); misfolded protein (M); BiP; Translocation Pore (Sec61); Sec63; size 2 aggregate (A2); size 3 aggregate (A3); size 4 aggregate (A4).
Figure 3.
Background colors represent translocation (orange), unfolding (green), misfolding (yellow), and aggregation/disaggregation (red) modules. Additional states and reactions involving the luminal co-chaperone Scj1 are accounted for in the aggregation, unfolded, and misfolded modules, but are omitted from this diagram due to space limitations. Species are represented as follows: Pore; nascent protein (N), sliding state (x); folded protein (F); unfolded protein (U); misfolded protein (M); BiP; Sec63; size 2 aggregate (A2); size 3 aggregate (A3); size 4 aggregate (A4). Sliding states (x) mimic the movement of the nascent protein further into the lumen.
Figure 4.
Folding efficiency vs. BiP binding rate without cooperativity.
Comparison of the folding efficiency (i.e. fraction of proteins folded) as a function of the binding rate between BiP and unfolded proteins. In this scenario, there is no cooperative effect among chaperones in folding, unfolding, or disaggregating proteins. The model number refers to the number of binding sites. In this scenario, Model 1 has the highest folding efficiency, followed by Models 2, 3 and 4.
Figure 5.
Protein coverage of the four models relative to Model 1 in the noncooperative scenario. Coverage refers to the percentage of proteins that are protected from misfolded and aggregation at any one time.
Figure 6.
Time series of the amount of bound protein for the different models, showing greater coverage for the single binding site model.
Figure 7.
Folding efficiency vs. BiP binding rate with cooperativity.
Comparison of the folding efficiency (i.e. fraction of proteins folded) as a function of the binding rate between BiP and unfolded proteins with a cooperativity factor of C = 10. In this scenario, Model 2 has the highest folding efficiency.
Figure 8.
Folding efficiency vs. cooperativity.
Folding efficiency of the four models as a function of the cooperativity factor.
Figure 9.
Folding efficiency vs. number of BiP molecules.
Comparison of the folding efficiency as a function of the number of BiP molecules with no cooperativity and U = 1.0 · 106 molecules. In this scenario, Model 1 folds most efficiently.
Figure 10.
Folding efficiency vs. number of BiP molecules, cooperative scenario.
Folding efficiency of the four models as a function of BiP concentration with cooperativity factor C = 10. In this scenario, Model 2 folds most efficiently.
Figure 11.
Comparison of the BiP cost of the four models for both non-cooperative and cooperative scenarios. It is better to have lower chaperone cost so that fewer chaperones are required.
Figure 12.
Map of the parameter study indentifies effects of varying 7 parameters with respect to protein folding efficiency.
Figure 13.
Folding efficiency vs. translocation rate.
Folding efficiency as a function of translocation flux.