Length-dependent stability and strand length limits in antiparallel -sheet secondary structure

H. E. Stanger, F. A. Syud, J. F. Espinosa, I. Giriat, T. Muir, S. H. Gellman
2001 Proceedings of the National Academy of Sciences of the United States of America  
Designed peptides that fold autonomously to specific conformations in aqueous solution are useful for elucidating protein secondary structural preferences. For example, autonomously folding model systems have been essential for establishing the relationship between ␣-helix length and ␣-helix stability, which would be impossible to probe with ␣-helices embedded in folded proteins. Here, we use designed peptides to examine the effect of strand length on antiparallel ␤-sheet stability. ␣-Helices
more » ... come more stable as they grow longer. Our data show that a two-stranded ␤-sheet ("␤-hairpin") becomes more stable when the strands are lengthened from five to seven residues, but that further strand lengthening to nine residues does not lead to further ␤-hairpin stabilization for several extension sequences examined. (In one case, all-threonine extension, there may be an additional stabilization on strand lengthening from seven to nine residues.) These results suggest that there may be an intrinsic limit to strand length for most sequences in antiparallel ␤-sheet secondary structure. NMR. NMR experiments were performed as described earlier. Most data were acquired on a Varian INOVA 500 MHz spectrometer at 277 K; additional nuclear Overhauser effect (NOE) spectroscopy and rotating-frame Overhauser effect spectroscopy (ROESY) data were obtained for D P and c( D P) 2 by using a Bruker (Billerica, MA) AVANCE 750 MHz spectrometer, and for D P-TT 2 by using a Varian 600 MHz spectrometer at 277 K. Pulsed-field gradient phase-sensitive heteronuclear sequential quantum correlation (HSQC) experiments were carried out by using the "gHSQC" pulse sequence provided by Varian. A spectral window of 27,000 Hz was used for the carbon-13 dimension, which was externally referenced to 2,2-dimethyl-2silapentane-5-sulfonate. NOE-Restrained Dynamics. Simulations were performed for D P-TT 2 by using the program DYANA (31). NOE restraints were This paper was submitted directly (Track II) to the PNAS office. Abbreviations: NOE, nuclear Overhauser effect; ROESY, rotating frame Overhauser effect spectroscopy.
doi:10.1073/pnas.211536998 pmid:11593011 pmcid:PMC59824 fatcat:7d5h57k7erhq5mpy4wzu7eruwq