What distinguishes GroEL substrates from other Escherichiacoli proteins?

• Published in: The FEBS journal Vol. 279; no. 4; pp. 543 - 550
• Main Authors: Azia, Ariel, Unger, Ron, Horovitz, Amnon
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01-02-2012
• Subjects: Cellular biology; E coli; Protein folding; Substrates
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/j.1742-4658.2011.08458.x

Experimental studies and theoretical considerations have shown that only a small subset of Escherichiacoli proteins fold invivo with the help of the GroE chaperone system. These proteins, termed GroE substrates, have been divided into three classes: (a) proteins that can fold independently, but are found to associate with GroEL; (b) proteins that require GroE when the cell is under stress; and (c) 'obligatory' proteins that require GroE assistance even under normal conditions. It remains unclear, however, why some proteins need GroE and others do not. Here, we review experimental and computational studies that addressed this question by comparing the sequences and structural, biophysical and evolutionary properties of GroE substrates with those of nonsubstrates. In general, obligatory substrates are found to have lower folding propensities and be more aggregation prone. GroE substrates are also more conserved than other proteins and tend to utilize more optimal codons, but this latter feature is less apparent for obligatory substrates. There is no evidence, however, for any specific sequence signatures although there is a tendency for sequence periodicity. Our review shows that reliable sequence- or structure-based predictions of GroE dependency remain a challenge. We suggest that the different classes of GroE substrates be studied separately and that proper control test sets (e.g. TIM barrel proteins that need GroE for folding versus TIM barrels that fold independently) be used more extensively in such studies. Only a small subset of E.coli proteins require the GroE chaperone system for folding invivo under normal conditions. It remains unclear, however, why some proteins need GroE and others do not. Here, we review experimental and computational studies that compared various properties of GroE substrates with those of non-substrates and show that predicting GroE-dependency remains a challenge. [PUBLICATION ABSTRACT]