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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 
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. 
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 
ProteomicsStructural basis for lipid binding and function by an evolutionally conserved protein, Serum Amyloid A
Serum amyloid A (SAA) is a plasma protein that transports lipids during inflammation. To explore SAA solution conformations and lipid binding mechanism, we used hydrogen-deuterium exchange mass spectrometry, lipoprotein reconstitution, sequence analysis and molecular dynamics simulations. Solution ...
ORGANISM(S): Mus musculus (Mouse) 
2020-02-17 | PXD016391 | Pride
Hydrogen-deuterium exchange mass spectrometry  molecular dynamics simulations  lipoprotein nanoparticle  intrinsically disordered protein  β-hairpin misfolding intermediate  inflammation and immunity 
ProteomicsGeneral structural features that regulate integrin affinity revealed by atypical αVβ8
Integrins αVβ8 and αVβ6 are master activators of proTGF-βs. Whereas most integrins including αVβ6 are activated by tensile force applied by the cytoskeleton, αVβ8 links differently to the cytoskeleton and lacks the open headpiece conformation that represents the high affinity state of other integrin...
ORGANISM(S): Homo sapiens (Human) 
2019-12-03 | PXD014348 | Pride
Integrin Conformational change Affinity Protgf-β Hydrogen deuterium exchange Crystal structure 
ProteomicsProtection of the prodomain α1-helix correlates with latency in the transforming growth factor-β family
The 33 members of the transforming growth factor beta (TGF-β) family are fundamentally important for organismal development and homeostasis. Family members are synthesized and secreted as pro-complexes of non-covalently associated prodomains and growth factors (GF). Pro-complexes from a subset of fa...
ORGANISM(S): Homo sapiens (Human) 
2022-01-19 | PXD026841 | Pride
Transforming growth factor beta (tgf‐β) Bone morphogenetic protein (bmp) Electron microscopy (em) Hydrogen exchange mass spectrometry Activin 
ProteomicsThe heme regulatory motifs of heme oxygenase-2 function to transfer heme to the catalytic site for degradation
Heme regulatory motifs (HRMs) are found in a variety of proteins that are involved in diverse biological functions. In the C-terminal tail region of human heme oxygenase-2 (HO2), there are two HRMs whose cysteines form a disulfide bond; when reduced, these cysteines are available to bind Fe3+-heme. ...
ORGANISM(S): Homo sapiens (Human) 
2020-03-18 | PXD017538 | Pride
Enzyme mechanisms  enzyme kinetics  protein dynamics  conformational change  hydrogen deuterium exchange  hdxms 
UnknownDynamic Allostery Mediated by a Conserved Tryptophan in the Tec Family Kinases.
Not available
S-EPMC4807093 | biostudies-literature
ProteomicsAn SH3-binding allosteric modulator stabilizes the global conformation of the AML-associated Src-family kinase, Hck
While ATP-site inhibitors for protein-tyrosine kinases are often effective drugs, their clinical utility can be limited by off-target activity and acquired resistance mutations due to the conserved nature of the ATP-binding site. However, combining ATP-site and allosteric kinase inhibitors can overc...
ORGANISM(S): Homo sapiens (Human) 
2025-05-07 | PXD054878 | Pride
Hck  hdx-ms  hydrogen/deuterium exchange mass spectrometry  allosteric modulator  global conformation 
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