Structural biology: analysis of 'downhill' protein folding.
There is controversy as to whether homologues from the peripheral subunit binding domain family of small proteins fold 'downhill' (that is, non-cooperatively, in the absence of free-energy barriers between conformations) and whether they modulate their size for biological function. Sadqi et al. claim that Naf-BBL--a naphthylalanine-labelled, truncated version of this domain--folds in this way, on the grounds that they recorded a wide spread of melting temperatures of individual atoms measured by proton nuclear magnetic resonance (NMR) during their thermal denaturation. But their data are not of adequate quality to distinguish, within experimental error, between downhill folding and folding with a cooperative transition. Accordingly, their results offer no compelling evidence that Naf-BBL folds downhill, particularly as non-truncated, unmodified peripheral subunit binding domains seem to fold cooperatively.
Ferguson
Neil
N
Medical Research Council Centre for Protein Engineering, Medical Research Council Centre, Cambridge CB2 2QH, UK. arf25@cam.ac.uk
Sharpe
Timothy D
TD
Johnson
Christopher M
CM
Schartau
Pamela J
PJ
Fersht
Alan R
AR
D000494:Allosteric Regulation; D016477:Artifacts; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D012107:Research Design; D013816:Thermodynamics; D044366:Transition Temperature