PAS domain receptor photoactive yellow protein is converted to a molten globule state upon activation.
Biological signaling generally involves the activation of a receptor protein by an external stimulus followed by protein-protein interactions between the activated receptor and its downstream signal transducer. The current paradigm for the relay of signals along a signal transduction chain is that it occurs by highly specific interactions between fully folded proteins. However, recent results indicate that many regulatory proteins are intrinsically unstructured, providing a serious challenge to this paradigm and to the nature of structure-function relationships in signaling. Here we study the structural changes that occur upon activation of the blue light receptor photoactive yellow protein (PYP). Activation greatly reduces the tertiary structure of PYP but leaves the level secondary structure largely unperturbed. In addition, activated PYP exposes previously buried hydrophobic patches and allows significant solvent penetration into the core of the protein. These traits are the distinguishing hallmarks of molten globule states, which have been intensively studied for their role in protein folding. Our results show that receptor activation by light converts PYP to a molten globule and indicate stimulus-induced unfolding to a partially unstructured molten globule as a novel theme in signaling.
Lee
B C
BC
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA.
Croonquist
P A
PA
Sosnick
T R
TR
Hoff
W D
WD
D020106:Acrylamide / Q000494:pharmacology; D000817:Anilino Naphthalenesulfonates; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism; D004926:Escherichia coli; D005456:Fluorescent Dyes; D007700:Kinetics; D008027:Light; D020283:Photoreceptors, Microbial; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry
D000817:Anilino Naphthalenesulfonates; D001426:Bacterial Proteins; D005456:Fluorescent Dyes; D020283:Photoreceptors, Microbial; D011994:Recombinant Proteins; C050162:photoactive yellow protein, Bacteria; D020106:Acrylamide; C027132:1-anilino-8-naphthalenesulfonate