Folding without charges
2012 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 15, 5705-5710 p.Article in journal (Refereed) Published
Surface charges of proteins have in several cases been found to function as structural gatekeepers, which avoid unwanted interactions by negative design, for example, in the control of protein aggregation and binding. The question is then if side-chain charges, due to their desolvation penalties, play a corresponding role in protein folding by avoiding competing, misfolded traps? To find out, we removed all 32 side-chain charges from the 101-residue protein S6 from Thermus thermophilus. The results show that the charge-depleted S6 variant not only retains its native structure and cooperative folding transition, but folds also faster than the wild-type protein. In addition, charge removal unleashes pronounced aggregation on longer timescales. S6 provides thus an example where the bias toward native contacts of a naturally evolved protein sequence is independent of charges, and point at a fundamental difference in the codes for folding and intermolecular interaction: specificity in folding is governed primarily by hydrophobic packing and hydrogen bonding, whereas solubility and binding relies critically on the interplay of side-chain charges.
Place, publisher, year, edition, pages
2012. Vol. 109, no 15, 5705-5710 p.
folding cooperativity, protein aggregation, protein charges, protein engineering, protein folding
Biophysics Biochemistry and Molecular Biology
Research subject Biophysics; Biochemistry
IdentifiersURN: urn:nbn:se:su:diva-76060DOI: 10.1073/pnas.1118640109ISI: 000302533500035OAI: oai:DiVA.org:su-76060DiVA: diva2:525590
Author count: 4;2012-05-082012-05-082012-09-24Bibliographically approved