The effect of backbone cyclization on the thermodynamics of beta-sheet unfolding: stability optimization of the PIN WW domain.
Backbone cyclization is often used in attempts to enhance protein stability, but is not always successful as it is possible to remove stabilizing or introduce destabilizing interactions in the process. Cyclization of the PIN1 WW domain, a 34-residue three-stranded beta-sheet structure, removes a favorable electrostatic interaction between its termini. Nevertheless, optimization of the linker connecting the N- and C-termini using information based on the previously determined ensemble of NMR structures leads to beta-sheets that are more stable than those derived from the linear sequence. Linkers that are too short or too long introduce strain, likely disrupting native interactions, leading to cyclic folds that are less stable than that of the linear sequence.
Deechongkit
Songpon
S
Department of Chemistry and The Skaggs Institute of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC 506, La Jolla, California 92037, USA.
Kelly
Jeffery W
JW
D000595:Amino Acid Sequence; D004795:Enzyme Stability; D007700:Kinetics; D008969:Molecular Sequence Data; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000138:chemical synthesis / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013816:Thermodynamics
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase