ArticleJournal of the American Chemical Society2013
Allosteric activation of the Par-6 PDZ via a partial unfolding transition.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- Allosteric Signaling in PDZ Energetic Networks: Embedding Error Analysis.The journal of physical chemistry. B · 2023Article
- Phosphorylation-induced changes in the PDZ domain of Dishevelled 3.Scientific reports · 2021Article
- Spectral analysis of molecular dynamics simulations on PDZ: MD sectors.Journal of biomolecular structure & dynamics · 2020Article
- Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition.International review of cell and molecular biology · 2019Review
- Distinct Roles for Conformational Dynamics in Protein-Ligand Interactions.Structure (London, England : 1993) · 2016Article
- Correction to Binding of Crumbs to the Par-6 CRIB-PDZ Module Is Regulated by Cdc42.Biochemistry · 2016Article
- Binding of Crumbs to the Par-6 CRIB-PDZ Module Is Regulated by Cdc42.Biochemistry · 2016Article
- Some (dis)assembly required: partial unfolding in the Par-6 allosteric switch.Biophysical reviews · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Proteins exist in a delicate balance between the native and unfolded states, where thermodynamic stability may be sacrificed to attain the flexibility required for efficient catalysis, binding, or allosteric control. Partition-defective 6 (Par-6) regulates the Par polarity complex by transmitting a GTPase signal through the Cdc42/Rac interaction binding PSD-95/Dlg/ZO-1 (CRIB-PDZ) module that alters PDZ ligand binding. Allosteric activation of the PDZ is achieved by local rearrangement of the L164 and K165 side chains to stabilize the interdomain CRIB:PDZ interface and reposition a conserved element of the ligand binding pocket. However, microsecond to millisecond dynamics measurements revealed that L164/K165 exchange requires a larger rearrangement than expected. The margin of thermodynamic stability for the PDZ domain is modest (∼3 kcal/mol) and further reduced by transient interactions with the disordered CRIB domain. Measurements of local structural stability revealed that tertiary contacts within the PDZ are disrupted by a partial unfolding transition that enables interconversion of the L/K switch. The unexpected participation of partial PDZ unfolding in the allosteric mechanism of Par-6 suggests that native-state unfolding may be essential for the function of other marginally stable proteins.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.