Peter E. Wright
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View article: Discovery of a Cryptic Pocket in <i>Ec</i> DsbA Opens New Opportunities for Antibacterial Discovery
Discovery of a Cryptic Pocket in <i>Ec</i> DsbA Opens New Opportunities for Antibacterial Discovery Open
We have used nuclear magnetic resonance (NMR) spectroscopy to characterize dynamics in the bacterial oxidoreductase enzyme Escherichia coli disulfide bond protein A ( Ec DsbA). Through this process we identified a cryptic pocket in the str…
View article: Linker Length and Composition within Disordered Binding Motifs Modulates the Avidity and Reversibility of a Multivalent Protein Interaction Switch
Linker Length and Composition within Disordered Binding Motifs Modulates the Avidity and Reversibility of a Multivalent Protein Interaction Switch Open
Intrinsically disordered proteins that mediate the cellular transcriptional response to hypoxia play important roles in regulating oxygen stress genes. The feedback inhibitor CITED2 operates a unidirectional switch that efficiently termina…
View article: Mechanism of inhibition of acid-mediated transthyretin aggregation by designed peptides
Mechanism of inhibition of acid-mediated transthyretin aggregation by designed peptides Open
View article: Switchable client specificity in a dual functional chaperone coordinates light-harvesting complex biogenesis
Switchable client specificity in a dual functional chaperone coordinates light-harvesting complex biogenesis Open
The proper assembly of light-harvesting complexes (LHCs) is critical for photosynthesis and requires the biogenesis of light-harvesting chlorophyll a , b -binding proteins (LHCPs) to be coordinated with chlorophyll (Chl) biosynthesis. The …
View article: Linker Length and Composition within Disordered Binding Motifs modulates the Avidity and Reversibility of a Multivalent Protein Interaction Switch
Linker Length and Composition within Disordered Binding Motifs modulates the Avidity and Reversibility of a Multivalent Protein Interaction Switch Open
Intrinsically disordered proteins that mediate the cellular transcriptional response to hypoxia play important roles in turning on and turning off oxygen stress genes. In particular, the feedback inhibitor CITED2 operates a unidirectional …
View article: Ligand binding into a cryptic pocket in Escherichia coli DsbA inhibits the enzymatic activity in vitro
Ligand binding into a cryptic pocket in Escherichia coli DsbA inhibits the enzymatic activity in vitro Open
Disulfide bond protein A (DsbA) plays a pivotal role in catalysing the formation of disulfide bonds within the periplasm of most Gram-negative bacteria. As this process is required for the folding of multiple virulence-associated proteins,…
View article: Initiation of transthyretin aggregation at neutral pH by fluid agitation
Initiation of transthyretin aggregation at neutral pH by fluid agitation Open
The transthyretin (TTR) tetramer, assembled as a dimer of dimers, transports thyroxine and retinol binding protein in blood plasma and cerebrospinal fluid. Aggregation of wild type (WT) or pathogenic variant TTR leads to transthyretin amyl…
View article: Switchable client specificity in a dual functional chaperone coordinates light harvesting complex biogenesis
Switchable client specificity in a dual functional chaperone coordinates light harvesting complex biogenesis Open
The proper assembly of light harvesting complexes (LHCs) is critical for photosynthesis and requires the biogenesis of light-harvesting chlorophyll a,b-binding proteins (LHCPs) to be coordinated with the biosynthesis of chlorophylls (Chl).…
View article: Aggregation of Transthyretin by Fluid Agitation
Aggregation of Transthyretin by Fluid Agitation Open
The transthyretin (TTR) tetramer, assembled as a dimer of dimers, transports thyroxine and retinol binding protein in blood plasma and cerebrospinal fluid. Aggregation of wild type or pathogenic variant TTR leads to transthyretin amyloidos…
View article: Mispacking of the <scp>F87</scp> sidechain drives aggregation‐promoting conformational fluctuations in the subunit interfaces of the transthyretin tetramer
Mispacking of the <span>F87</span> sidechain drives aggregation‐promoting conformational fluctuations in the subunit interfaces of the transthyretin tetramer Open
Aberrant formation and deposition of human transthyretin (TTR) aggregates causes transthyretin amyloidosis. To initialize aggregation, transthyretin tetramers must first dissociate into monomers that partially unfold to promote entry into …
View article: Conformational Dynamics of an Amyloidogenic Intermediate of Transthyretin: Implications for Structural Remodeling and Amyloid Formation
Conformational Dynamics of an Amyloidogenic Intermediate of Transthyretin: Implications for Structural Remodeling and Amyloid Formation Open
View article: Mispacking of the F87 sidechain drives aggregation-promoting conformational fluctuations in the subunit interfaces of the transthyretin tetramer
Mispacking of the F87 sidechain drives aggregation-promoting conformational fluctuations in the subunit interfaces of the transthyretin tetramer Open
Aberrant formation and deposition of human transthyretin (TTR) aggregates causes transthyretin amyloidosis. To initialize aggregation, transthyretin tetramers must first dissociate into monomers that partially unfold to promote entry into …
View article: Characterization of an amyloidogenic intermediate of transthyretin by NMR relaxation dispersion
Characterization of an amyloidogenic intermediate of transthyretin by NMR relaxation dispersion Open
The aggregation pathway of transthyretin (TTR) proceeds through rate-limiting dissociation of the tetramer and partial misfolding of the monomers, which assemble into amyloid structures through a downhill polymerization mechanism. The stru…
View article: Conformational Dynamics of an Amyloidogenic Intermediate of Transthyretin: Implications for Structural Remodeling and Amyloid Formation
Conformational Dynamics of an Amyloidogenic Intermediate of Transthyretin: Implications for Structural Remodeling and Amyloid Formation Open
View article: Probing the Dissociation Pathway of a Kinetically Labile Transthyretin Mutant
Probing the Dissociation Pathway of a Kinetically Labile Transthyretin Mutant Open
Aggregation of transthyretin (TTR) is associated with devastating amyloid diseases. Amyloidosis begins with the dissociation of the native homotetramer (a dimer of dimers) to form a monomeric intermediate that assembles into pathogenic agg…
View article: Glutamine-rich regions of the disordered CREB transactivation domain mediate dynamic intra- and intermolecular interactions
Glutamine-rich regions of the disordered CREB transactivation domain mediate dynamic intra- and intermolecular interactions Open
The cyclic AMP response element (CRE) binding protein (CREB) is a transcription factor that contains a 280-residue N-terminal transactivation domain and a basic leucine zipper that mediates interaction with DNA. The transactivation domain …
View article: The smallest functional antibody fragment: Ultralong CDR H3 antibody knob regions potently neutralize SARS-CoV-2
The smallest functional antibody fragment: Ultralong CDR H3 antibody knob regions potently neutralize SARS-CoV-2 Open
Cows produce antibodies with a disulfide-bonded antigen-binding domain embedded within ultralong heavy chain third complementarity determining regions. This “knob” domain is analogous to natural cysteine-rich peptides such as knottins in t…
View article: Probing the dissociation pathway of a kinetically labile transthyretin mutant
Probing the dissociation pathway of a kinetically labile transthyretin mutant Open
Aggregation of transthyretin (TTR) is associated with devastating TTR amyloid disease. Amyloidosis begins with dissociation of the native tetramer to form a monomeric intermediate that assembles into pathogenic aggregates. This process is …
View article: From Immunogenic Peptides to Intrinsically Disordered Proteins
From Immunogenic Peptides to Intrinsically Disordered Proteins Open
It is hard to evaluate the role of individual mentors in the genesis of important ideas. In the case of our realization that proteins do not have to be stably folded to be functional, the influence of Richard Lerner and our collaborative w…
View article: Role of conformational dynamics in pathogenic protein aggregation
Role of conformational dynamics in pathogenic protein aggregation Open
View article: Multilayer Perceptron Analysis of Radiomics to Predict Local Recurrence of Lung Cancer After Radiotherapy
Multilayer Perceptron Analysis of Radiomics to Predict Local Recurrence of Lung Cancer After Radiotherapy Open
Purpose: to assess the likelihood of local recurrence of lung malignancies following stereotactic ablative radiotherapy (SABR) by evaluating clinical and radiomic features with machine learning and novel use of deep learning methods.
Meth…
View article: Coupling of binding and differential subdomain folding of the intrinsically disordered transcription factor <scp>CREB</scp>
Coupling of binding and differential subdomain folding of the intrinsically disordered transcription factor <span>CREB</span> Open
The cyclic AMP response element binding protein (CREB) contains a basic leucine zipper motif (bZIP) that forms a coiled coil structure upon dimerization and specific DNA binding. Although this state is well characterized, key features of C…
View article: Mapping Interactions of the Intrinsically Disordered C-Terminal Regions of Tetrameric p53 by Segmental Isotope Labeling and NMR
Mapping Interactions of the Intrinsically Disordered C-Terminal Regions of Tetrameric p53 by Segmental Isotope Labeling and NMR Open
The C-terminal region of the tumor suppressor protein p53 contains three domains, nuclear localization signal (NLS), tetramerization domain (TET), and C-terminal regulatory domain (CTD), which are essential for p53 function. Characterizati…
View article: Transient On- and Off-Pathway Protein Folding Intermediate States Characterized with NMR Relaxation Dispersion
Transient On- and Off-Pathway Protein Folding Intermediate States Characterized with NMR Relaxation Dispersion Open
The earliest events in the folding of a protein are in general poorly understood. We used NMR R2 relaxation dispersion experiments to study transient local collapse events in the unfolded-state (U) conformational ensemble…
View article: Structural and dynamic studies of DNA recognition by NF-κB p50 RHR homodimer using methyl NMR spectroscopy
Structural and dynamic studies of DNA recognition by NF-κB p50 RHR homodimer using methyl NMR spectroscopy Open
Protein dynamics involving higher-energy sparsely populated conformational substates are frequently critical for protein function. This study describes the dynamics of the homodimer (p50)2 of the p50 Rel homology region (RHR) of the transc…
View article: A transthyretin monomer intermediate undergoes local unfolding and transient interaction with oligomers in a kinetically concerted aggregation pathway
A transthyretin monomer intermediate undergoes local unfolding and transient interaction with oligomers in a kinetically concerted aggregation pathway Open
View article: Interactions of a Long Noncoding RNA with Domains of NF-κB and IκBα: Implications for the Inhibition of Non-Signal-Related Phosphorylation
Interactions of a Long Noncoding RNA with Domains of NF-κB and IκBα: Implications for the Inhibition of Non-Signal-Related Phosphorylation Open
The transcription factor NF-κB is one of the central mediators of cellular signaling pathways. Under resting conditions, the canonical RelA-p50 (p65-p50) heterodimer NF-κB remains sequestered in the cytoplasm in complex with its inhibitor …
View article: Structural biology - Painting the mechanistic landscape of biomolecules
Structural biology - Painting the mechanistic landscape of biomolecules Open
View article: Characterization of the High-Affinity Fuzzy Complex between the Disordered Domain of the E7 Oncoprotein from High-Risk HPV and the TAZ2 Domain of CBP
Characterization of the High-Affinity Fuzzy Complex between the Disordered Domain of the E7 Oncoprotein from High-Risk HPV and the TAZ2 Domain of CBP Open
The intrinsically disordered N-terminal region of the E7 protein from high-risk human papillomavirus (HPV) strains is responsible for oncogenic transformation of host cells through its interaction with a number of cellular factors, includi…
View article: The molecular basis of allostery in a facilitated dissociation process
The molecular basis of allostery in a facilitated dissociation process Open