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ProteomicsTranslocation of polyubiquitinated protein substrates by the hexameric Cdc48 ATPase
The hexameric Cdc48 ATPase (p97 or VCP in mammals) cooperates with its cofactor Ufd1/Npl4 to extract polyubiquitinated proteins from membranes or macromolecular complexes for degradation by the proteasome. Here, we clarify how the Cdc48 complex unfolds its substrates and translocates polypeptides wi...
ORGANISM(S): Saccharomyces cerevisiae (Baker's yeast) 
2022-01-19 | PXD027639 | Pride
Hydrogen deuterium exchange mass spectrometry Npl4 Unfolding Ufd1 Translocation Ubiquitin Vcp Hdx-ms P97 Aaa atpase 
ProteomicsStructural mechanism of a drug-binding process involving a large conformational change of the protein target
Structural biology studies indicate that proteins often undergo large conformational changes when binding small molecules, but atomic-level descriptions of binding events involving such changes have been elusive. A prominent example of binding accompanied by a large conformational change is the bind...
ORGANISM(S): Homo sapiens (Human) 
2023-04-07 | PXD034008 | Pride
Hdx ms Hydrogen exchange mass spectrometry Molecular dynamics simulations  drug binding  abl kinase  localized unfolding  imatinib resistance 
ProteomicsDynamics of integrin α5β1, fibronectin, and their complex
Integrin α5β1 mediates cell adhesion to the extracellular matrix (ECM) by binding fibronectin (Fn). Selectivity for Fn by α5β1 is achieved through recognition of an RGD motif in the 10th type-III Fn domain (Fn10) and the synergy site in the 9th type-III Fn domain (Fn9). However, details of the inter...
ORGANISM(S): Homo sapiens (Human) 
2022-08-09 | PXD031508 | Pride
Integrin Thermal stability Conformational change Hydrogen deuterium exchange Fibronectin Affinity 
ProteomicsThe conformational state of PLCγ cSH2-linker contributes to Ibrutinib resistance
Mutations in PLCγ, a substrate of the tyrosine kinase BTK, are often found in patients who develop resistance to the BTK inhibitor Ibrutinib. However, the mechanisms by which these PLCγ mutations cause Ibrutinib resistance are unclear. Under normal signaling conditions, BTK mediated phosphorylation ...
ORGANISM(S): Rattus norvegicus (Rat) 
2022-01-19 | PXD028923 | Pride
Plcγ  phospholipase c gamma  ibrutinib resistance  allostery  hdx-ms  hydrogen/deuterium exchange mass spectrometry  nmr  sh2 domain. 
ProteomicsATP-site inhibitors induce unique conformations of the Src-family kinase, Fgr
Src family kinases are often overexpressed and constitutively active in cancer cells, where they represent promising targets for therapeutic intervention. In myeloid hematopoietic cells, Hck, Lyn, and Fgr are associated with both chronic and acute forms of myeloid leukemia. All three of these kinase...
ORGANISM(S): Homo sapiens (Human) 
2022-09-22 | PXD032014 | Pride
Src-family kinase  acute myeloid leukemia  hdx ms  hydrogen/deuterium exchange mass spectrometry 
ProteomicsResolving chaperone-assisted protein folding on the ribosome at the peptide level
The cellular environment is critical for efficient protein maturation, but how proteins fold during biogenesis remains poorly understood. We used hydrogen/deuterium exchange (HDX) mass spectrometry (MS) to define, at peptide resolution, the cotranslational chaperone-assisted folding pathway of Esche...
ORGANISM(S): Escherichia coli 
2024-07-12 | PXD036945 | Pride
Hdxms  hydrogen deuterium exchange mass spectrometry  protein folding  chaperone  ribosome  trigger factor  dhfr  cotranslational folding 
ProteomicsCovalent Inhibition of Pro-Apoptotic BAX
BCL-2-associated X protein (BAX) is a promising therapeutic target for activating or restraining apoptosis in diseases of pathologic cell survival or cell death, respectively. In response to cellular stress, BAX transforms from a quiescent cytosolic monomer into a toxic oligomer that permeabilizes t...
ORGANISM(S): Homo sapiens (Human) 
2024-01-19 | PXD040917 | Pride
Bax  hdx-ms  hydrogen/deuterium exchange mass spectrometry  covalent inhibitor 
ProteomicsVon Willebrand factor A1 domain affinity for GPIbα and stability are differentially regulated by its O-glycosylated N-linker and C-linker
Hemostasis in the arterial circulation is mediated by binding of the A1 domain of the ultralong protein von Willebrand factor to GPIbα on platelets to form a platelet plug. A1 is activated by tensile force on VWF concatemers imparted by hydrodynamic drag force. The A1 core is protected from force-in...
ORGANISM(S): Homo sapiens (Human) 
2022-05-09 | PXD029942 | Pride
Mucin Protein stability Hdxms Von willebrand factor Conformational change Glycoprotein Hydrogen deuterium exchange Intrinsically disordered protein 
ProteomicsIrisin acts through its integrin receptor in a novel two-step process
Exercise benefits the human body in many ways. Irisin is secreted by muscle, increased with exercise, and conveys many physiological benefits, including improved cognition and resistance to neurodegeneration. Irisin acts via αV integrins; however, a mechanistic understanding of how small polypeptide...
ORGANISM(S): Homo sapiens (Human) 
2023-06-04 | PXD035397 | Pride
Irisin  integrin  hdx-ms  hydrogen/deuterium exchange mass spectrometry  polypeptide hormone  αvβ5 
ProteomicsStructural Basis for Defective Membrane Targeting of Mutant Enzyme in Human VLCAD Deficiency
Very long-chain acyl-CoA dehydrogenase (VLCAD) is an inner mitochondrial membrane enzyme that catalyzes the first and rate-limiting step of long-chain fatty acid oxidation. Point mutations in human VLCAD can produce an inborn error of metabolism called VLCAD deficiency that can lead to severe pathop...
ORGANISM(S): Homo sapiens (Human) 
2022-06-29 | PXD029565 | Pride
Vlcad  fatty acid oxidation  membrane protein structure  hdx-ms  hydrogen/deuterium exchange mass spectrometry  x-ray crystallography  molecular dynamics 
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