Picometer-scale conformational heterogeneity separates functional from nonfunctional states of a photoreceptor protein.
Protein structural fluctuations occur over a wide spatial scale, ranging from minute, picometer-scale displacements, to large, interdomain motions and partial unfolding. While large-scale protein structural changes and their effects on protein function have been the focus of much recent attention, small-scale fluctuations have been less well studied, and are generally assumed to have proportionally smaller effects. Here we use the bacterial photoreceptor photoactive yellow protein (PYP) to test if subtle structural changes do, indeed, imply equally subtle functional effects. We flash froze crystals of PYP to trap the protein's conformational ensemble, and probed the molecules in this ensemble for their ability to facilitate PYP's biological function (i.e., light-driven isomerization of its chromophore). Our results indicate that the apparently homogeneous structural state observed in a 0.82 A crystal structure in fact comprises an ensemble of conformational states, in which subpopulations with nearly identical structures display dramatically different functional properties.
Department of Biochemistry, Brandeis University, 415 South Street, Waltham, MA 02453, USA.
Pierre-Damien
PD
Coureux
Zi Peng
ZP
Fan
Vivian
V
Stojanoff
Ulrich K
UK
Genick
D001426:Bacterial Proteins / Q000737:chemistry* / Q000528:radiation effects; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005615:Freezing; D007536:Isomerism; D008027:Light; D008958:Models, Molecular; D010777:Photochemistry; D020283:Photoreceptors, Microbial / Q000737:chemistry* / Q000528:radiation effects; D011487:Protein Conformation
D001426:Bacterial Proteins; D020283:Photoreceptors, Microbial; C050162:photoactive yellow protein, Bacteria