Conformational specificity of the chaperonin GroEL for the compact folding intermediates of α-lactalbumin Journal Article
| Authors: | Hayer-Hartl, M. K.; Ewbank, J. J.; Creighton, T. E.; Ulrich Hartl, F. |
| Article Title: | Conformational specificity of the chaperonin GroEL for the compact folding intermediates of α-lactalbumin |
| Abstract: | The chaperonin GroEL binds unfolded polypeptides, preventing aggregation, and then mediates their folding in an ATP-dependent process. To understand the structural features in non-native polypeptides recognized by GroEL, we have used a-lactalbumin (αLA) as a model substrate. αLA (14.2 kDa) is stabilized by four disulfide bonds and a bound Ca2+ ion, offering the possibility of trapping partially folded disulfide intermediates between the native and the fully unfolded state. The conformers of αLA with high affinity for GroEL are compact, containing up to three disulfide bonds, and have significant secondary structure, but lack stable tertiary structure and expose hydrophobic surfaces. Complex formation requires almost the complete αLA sequence and is strongly dependent on salts that stabilize hydrophobic interactions. Unfolding of αLA to an extended state as well as the burial of hydrophobic surface upon formation of ordered tertiary structure prevent the binding to GroEL. Interestingly, GroEL interacts only with a specific subset of the many partially folded disulfide intermediates of αLA and thus may influence in vitro the kinetics of the folding pathways that lead to disulfide bonds with native combinations. We conclude that the chaperonin interacts with the hydrophobic surfaces exposed by proteins in a flexible compact intermediate or molten globule state. |
| Keywords: | protein conformation; animals; protein protein interaction; protein binding; protein stability; bacterial proteins; peptide fragments; models, molecular; cattle; protein folding; protein secondary structure; protein tertiary structure; disulfides; polypeptide; calcium ion; heat-shock proteins; hydrophobicity; salts; binding kinetics; disulfide bond; priority journal; article; inorganic salt; groel; chaperonin; groel protein; lactalbumin; α-lactalbumin; molten globuie; alpha lactalbumin; iodoacetamide |
| Journal Title: | EMBO Journal |
| Volume: | 13 |
| Issue: | 13 |
| ISSN: | 0261-4189 |
| Publisher: | Wiley Blackwell |
| Date Published: | 1994-07-01 |
| Start Page: | 3192 |
| End Page: | 3202 |
| Language: | English |
| PROVIDER: | scopus |
| PMCID: | PMC395211 |
| PUBMED: | 7913682 |
| DOI: | 10.1002/j.1460-2075.1994.tb06618.x |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
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