Abstract
We compare the folding of representative members of a protein superfamily by experiment and simulation to investigate common features in folding mechanisms. The homeodomain superfamily of three-helical, single-domain proteins exhibits a spectrum of folding processes that spans the complete transition from concurrent secondary and tertiary structure formation (nucleation-condensation mechanism) to sequential secondary and tertiary formation (framework mechanism). The unifying factor in their mechanisms is that the transition state for (un)folding is expanded and very native-like, with the proportion and degree of formation of secondary and tertiary interactions varying. There is a transition, or slide, from the framework to nucleation-condensation mechanism with decreasing stability of the secondary structure. Thus, framework and nucleation-condensation are different manifestations of an underlying common mechanism.
References
45
Referenced
217
10.1021/bi990088x
10.1038/nature01428
10.1016/S0022-2836(02)00029-3
10.1002/pro.5560030413
10.1146/annurev.bi.59.070190.003215
10.1006/jmbi.1995.0616
10.1016/S0968-0004(02)00012-9
- Fersht A. R. (1999) Structure and Mechanism in Protein Science (Freeman New York).
10.1038/346440a0
10.1038/14890
10.1006/jmbi.1998.2548
10.1016/S0969-2126(01)00596-2
10.1006/jmbi.2001.4728
10.1038/14896
10.1038/14901
10.1006/jmbi.2000.3647
10.1073/pnas.96.26.14854
10.1093/nar/18.17.5019
10.1073/pnas.221467198
10.1073/pnas.250473497
- Levitt M. (1990) encad Computer Program for Energy Calculations and Dynamics (Molecular Applications Group Palo Alto CA).
10.1016/0010-4655(95)00049-L
10.1021/jp964020s
10.1073/pnas.93.24.13583
- Kell, G. S. (1967) J. Chem. Eng. 12, 66-68. / J. Chem. Eng. (1967)
10.1016/S0969-2126(98)00106-3
10.1021/bi00107a010
10.1016/S0065-3233(08)60401-5
10.1021/bi000200n
10.1016/S1359-0278(96)00036-3
10.1006/jmbi.1996.0793
10.1002/(SICI)1097-0282(19970415)41:5<495::AID-BIP2>3.0.CO;2-H
10.1016/0022-2836(92)90561-W
10.1038/340122a0
10.1073/pnas.97.4.1525
10.1073/pnas.91.22.10422
10.1016/S0959-440X(97)80002-4
10.1016/S0022-2836(02)00672-1
10.1073/pnas.91.22.10430
10.1006/jmbi.1996.0172
10.1006/jmbi.1996.0173
10.1038/1412
10.1006/jmbi.2001.4873
10.1073/pnas.221467398
10.1016/S0959-440X(02)00009-X
Dates
Type | When |
---|---|
Created | 21 years, 9 months ago (Nov. 16, 2003, 3:42 p.m.) |
Deposited | 3 years, 4 months ago (April 13, 2022, 4:57 a.m.) |
Indexed | 1 month ago (July 30, 2025, 10:26 a.m.) |
Issued | 21 years, 10 months ago (Oct. 31, 2003) |
Published | 21 years, 10 months ago (Oct. 31, 2003) |
Published Online | 21 years, 10 months ago (Oct. 31, 2003) |
Published Print | 21 years, 9 months ago (Nov. 11, 2003) |
@article{Gianni_2003, title={Unifying features in protein-folding mechanisms}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1835776100}, DOI={10.1073/pnas.1835776100}, number={23}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Gianni, Stefano and Guydosh, Nicholas R. and Khan, Faaizah and Caldas, Teresa D. and Mayor, Ugo and White, George W. N. and DeMarco, Mari L. and Daggett, Valerie and Fersht, Alan R.}, year={2003}, month=oct, pages={13286–13291} }