Abstract
AbstractHere we describe the NMR conformational study of a 20‐residue linear peptide designed to fold into a monomeric three‐stranded antiparallel β‐sheet in aqueous solution. Experimental and statistical data on amino acid β‐turn and β‐sheet propensities, cross‐strand side‐chain interactions, solubility criteria, and our previous experience with β‐hairpins were considered for a rational selection of the peptide sequence. Sedimentation equilibrium measurements and NMR dilution experiments provide evidence that the peptide is monomeric. Analysis of 1H and 13C‐NMR parameters of the peptide, in particular NOEs and chemical shifts, and comparison with data obtained for two 12‐residue peptides encompassing the N‐ and C‐segments of the designed sequence indicates that the 20‐residue peptide folds into the expected conformation. Assuming a two‐state model, the exchange kinetics between the β‐sheet and the unfolded peptide molecules is in a suitable range to estimate the folding rate on the basis of the NMR linewidths of several resonances. The time constant for the coil‐β‐sheet transition is of the order of several microseconds in the designed peptide. Future designs based on this peptide system are expected to contribute greatly to our knowledge of the many factors involved in β‐sheet formation and stability.
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Dates
Type | When |
---|---|
Created | 14 years, 11 months ago (Oct. 1, 2010, 9:44 a.m.) |
Deposited | 1 year, 10 months ago (Oct. 28, 2023, 3:04 p.m.) |
Indexed | 1 month ago (July 30, 2025, 10:52 a.m.) |
Issued | 26 years, 8 months ago (Jan. 1, 1999) |
Published | 26 years, 8 months ago (Jan. 1, 1999) |
Published Online | 16 years, 8 months ago (Dec. 31, 2008) |
Published Print | 26 years, 8 months ago (Jan. 1, 1999) |
@article{Alba_1999, title={De novo design of a monomeric three‐stranded antiparallel β‐sheet}, volume={8}, ISSN={1469-896X}, url={http://dx.doi.org/10.1110/ps.8.4.854}, DOI={10.1110/ps.8.4.854}, number={4}, journal={Protein Science}, publisher={Wiley}, author={Alba, Eva De and Santoro, Jorge and Rico, Manuel and Jiménez, M. Angeles}, year={1999}, month=jan, pages={854–865} }