Fig. 7: NCLE misfolding model highlights roles of chaperones, essentiality, and loop contacts. | Nature Communications

Fig. 7: NCLE misfolding model highlights roles of chaperones, essentiality, and loop contacts.

From: A widespread protein misfolding mechanism is differentially rescued in vitro by chaperones based on gene essentiality

Fig. 7

Proteins containing native non-covalent lasso entanglement (NCLEs) are more likely to misfold through a mechanism that has a loss of NCLE where the thread or the loop is structurally interdependent with a gain of a non-native NCLE. In the presence of chaperones, the misfolding of native NCLEs in essential proteins is, on average, rescued while it is not in non-essential proteins in part due to the enrichment of aromatic-aromatic and hydrophobic-aromatic loop forming contacts (F-F, F-Y, S-Y, H-C). We speculate this is due to chaperones DnaK and GroEL having to expend less energy in reopening the loop of essential proteins than non-essential proteins to allow for proper threading of the native NCLE. This diagram only displays misfolding pathways. There are, of course, other pathways involving on-pathway intermediates that are not shown in this model.

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