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PAS domain receptor photoactive yellow protein is converted to a molten globule state upon activation
B C Lee1, P A Croonquist, T R Sosnick
1Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA.
Abstract:
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.
Insights
Biological signaling often relies on specific protein interactions. This study reveals that light activation transforms the photoactive yellow protein (PYP) into a molten globule state, challenging traditional signaling paradigms.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Biological signaling typically involves specific interactions between fully folded proteins.
- Recent findings suggest intrinsically unstructured proteins challenge this paradigm.
- The structure-function relationship in signaling is under re-evaluation.
Purpose of the Study:
- To investigate the structural changes in photoactive yellow protein (PYP) upon activation.
- To explore the role of intrinsically unstructured proteins in biological signaling.
- To challenge the existing paradigm of signal transduction.
Main Methods:
- Studied the structural changes of photoactive yellow protein (PYP) upon light activation.
- Analyzed alterations in tertiary and secondary protein structure.
- Investigated exposure of hydrophobic patches and solvent penetration.
Main Results:
- Light activation significantly reduces PYP's tertiary structure.
- Secondary structure remains largely unperturbed.
- Activated PYP exhibits hallmarks of molten globule states, including exposed hydrophobic patches and core solvent penetration.
Conclusions:
- Receptor activation by light converts PYP into a molten globule state.
- Stimulus-induced unfolding to a partially unstructured molten globule is a novel signaling mechanism.
- This finding offers new insights into protein structure-function relationships in signaling pathways.