Hemmo Meyer
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View article: ATXN3 regulates lysosome regeneration after damage by targeting K48-K63-branched ubiquitin chains
ATXN3 regulates lysosome regeneration after damage by targeting K48-K63-branched ubiquitin chains Open
The cellular response to lysosomal damage involves fine-tuned mechanisms of membrane repair, lysosome regeneration and lysophagy, but how these different processes are coordinated is not fully understood. Here we show in human cells that t…
View article: Molecular Tweezers Block the Functional Pore of a Protein Machine
Molecular Tweezers Block the Functional Pore of a Protein Machine Open
We present symmetric multivalent tweezers as the first class of supramolecular elements designed to cover and functionally block a protein pore. As a model, we chose the enzyme p97, a hexameric AAA-ATPase that unfolds or segregates substra…
View article: 2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy
2024 VCP International Conference: Exploring multi-disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein, to the therapeutic advancement for VCP-associated multisystem proteinopathy Open
Valosin-containing protein (VCP/p97) is a ubiquitously expressed AAA+ ATPase associated with numerous protein-protein interactions and critical cellular functions including protein degradation and clearance, mitochondrial homeostasis, DNA …
View article: 2024 VCP International Conference: Exploring multi - disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein , to the therapeutic advancement for VCP - associated multisystem proteinopathy
2024 VCP International Conference: Exploring multi - disciplinary approaches from basic science of valosin containing protein, an AAA+ ATPase protein , to the therapeutic advancement for VCP - associated multisystem proteinopathy Open
Valosin-containing protein (VCP/p97) is a ubiquitously expressed AAA+ ATPase associated with numerous protein-protein interactions and critical cellular functions including protein degradation and clearance, mitochondrial homeostasis, DNA …
View article: Light‐Activatable Ubiquitin for Studying Linkage‐Specific Ubiquitin Chain Formation Kinetics
Light‐Activatable Ubiquitin for Studying Linkage‐Specific Ubiquitin Chain Formation Kinetics Open
Ubiquitination is a dynamic post‐translational modification governing protein abundance, function, and localization in eukaryotes. The Ubiquitin protein is conjugated to lysine residues of target proteins, but can also repeatedly be ubiqui…
View article: Alternating binding and p97-mediated dissociation of SDS22 and I3 recycles active PP1 between holophosphatases
Alternating binding and p97-mediated dissociation of SDS22 and I3 recycles active PP1 between holophosphatases Open
Protein phosphatase-1 catalytic subunit (PP1) joins diverse targeting subunits to form holophosphatases that regulate many cellular processes. Newly synthesized PP1 is known to be transiently sequestered in an inhibitory complex with Suppr…
View article: The Endo-Lysosomal Damage Response
The Endo-Lysosomal Damage Response Open
Lysosomes are the degradative endpoints of material delivered by endocytosis and autophagy and are therefore particularly prone to damage. Membrane permeabilization or full rupture of lysosomal or late endosomal compartments is highly dele…
View article: VCF1 is a p97/VCP cofactor promoting recognition of ubiquitylated p97-UFD1-NPL4 substrates
VCF1 is a p97/VCP cofactor promoting recognition of ubiquitylated p97-UFD1-NPL4 substrates Open
The hexameric AAA+ ATPase p97/VCP functions as an essential mediator of ubiquitin-dependent cellular processes, extracting ubiquitylated proteins from macromolecular complexes or membranes by catalyzing their unfolding. p97 is directed to …
View article: Modular DNA origami compartments for the engineering of a protein unfolding and degradation pathway
Modular DNA origami compartments for the engineering of a protein unfolding and degradation pathway Open
Within the cell, chemical reactions are often confined and organized through a modular architecture. This facilitates the targeted localization of molecular species and their efficient translocation to subsequent sites. Here, we present a …
View article: VCF1 is an unconventional p97/VCP cofactor promoting recognition of ubiquitylated p97-UFD1-NPL4 substrates
VCF1 is an unconventional p97/VCP cofactor promoting recognition of ubiquitylated p97-UFD1-NPL4 substrates Open
Summary The hexameric AAA+ ATPase p97/VCP functions as an essential mediator of ubiquitin-dependent cellular processes, extracting ubiquitylated proteins from macromolecular complexes or membranes by catalyzing their unfolding. p97 is dire…
View article: The UBX domain in UBXD1 organizes ubiquitin binding at the C-terminus of the VCP/p97 AAA-ATPase
The UBX domain in UBXD1 organizes ubiquitin binding at the C-terminus of the VCP/p97 AAA-ATPase Open
The AAA+ ATPase p97/VCP together with different sets of substrate-delivery adapters and accessory cofactor proteins unfolds ubiquitinated substrates to facilitate degradation by the proteasome. The UBXD1 cofactor is connected to p97-associ…
View article: Structural basis of ubiquitin‐independent <scp>PP1</scp> complex disassembly by p97
Structural basis of ubiquitin‐independent <span>PP1</span> complex disassembly by p97 Open
The AAA+‐ATPase p97 (also called VCP or Cdc48) unfolds proteins and disassembles protein complexes in numerous cellular processes, but how substrate complexes are loaded onto p97 and disassembled is unclear. Here, we present cryo‐EM struct…
View article: Targeting of client proteins to the VCP/p97/Cdc48 unfolding machine
Targeting of client proteins to the VCP/p97/Cdc48 unfolding machine Open
The AAA+ ATPase p97 (also called VCP or Cdc48) is a major protein unfolding machine with hundreds of clients in diverse cellular pathways that are critical for cell homeostasis, proliferation and signaling. In this review, we summarize rec…
View article: MAGED2 Is Required under Hypoxia for cAMP Signaling by Inhibiting MDM2-Dependent Endocytosis of G-Alpha-S
MAGED2 Is Required under Hypoxia for cAMP Signaling by Inhibiting MDM2-Dependent Endocytosis of G-Alpha-S Open
Mutations in MAGED2 cause transient Bartter syndrome characterized by severe renal salt wasting in fetuses and infants, which leads to massive polyhydramnios causing preterm labor, extreme prematurity and perinatal death. Notably, this con…
View article: Structural basis of ubiquitin-independent PP1 complex disassembly by p97
Structural basis of ubiquitin-independent PP1 complex disassembly by p97 Open
The AAA+ ATPase p97 (also called VCP, or Cdc48 in yeast) unfolds proteins and disassembles protein complexes in a myriad of cellular processes, but how a substrate complex needs to be loaded onto p97 by a dedicated substrate adapter and th…
View article: Zelkovamycin is an OXPHOS Inhibitory Member of the Argyrin Natural Product Family
Zelkovamycin is an OXPHOS Inhibitory Member of the Argyrin Natural Product Family Open
Natural products (NPs) are an important inspirational source for developing drugs and chemical probes. In 1999, the group of Ōmura reported the constitutional elucidation of zelkovamycin. Although largely unrecognized so far, this NP displ…
View article: Structure of the PUB Domain from Ubiquitin Regulatory X Domain Protein 1 (UBXD1) and Its Interaction with the p97 AAA+ ATPase
Structure of the PUB Domain from Ubiquitin Regulatory X Domain Protein 1 (UBXD1) and Its Interaction with the p97 AAA+ ATPase Open
AAA+ ATPase p97/valosin-containing protein (VCP)/Cdc48 is a key player in various cellular stress responses in which it unfolds ubiquitinated proteins to facilitate their degradation by the proteasome. P97 works in different cellular proce…
View article: Regulation of lysosome integrity and lysophagy by the ubiquitin-conjugating enzyme UBE2QL1
Regulation of lysosome integrity and lysophagy by the ubiquitin-conjugating enzyme UBE2QL1 Open
Lysosomal membrane permeabilization or full rupture of lysosomes is a common and severe stress condition that is relevant for degenerative disease, infection and cancer. Cells respond with extensive ubiquitination of damaged lysosomes, whi…
View article: VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle
VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle Open
Differentiated tissue is particularly vulnerable to alterations in protein and organelle homeostasis. The essential protein VCP, mutated in hereditary inclusion body myopathy, amyotrophic lateral sclerosis and frontotemporal dementia, is c…
View article: VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle
VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle Open
Differentiated tissue is particularly vulnerable to alterations in protein and organelle homeostasis. The essential protein VCP, mutated in hereditary inclusion body myopathy, amyotrophic lateral sclerosis and frontotemporal dementia, is c…
View article: VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle
VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle Open
Differentiated tissue is particularly vulnerable to alterations in protein and organelle homeostasis. The essential protein VCP, mutated in hereditary inclusion body myopathy, amyotrophic lateral sclerosis and frontotemporal dementia, is c…
View article: VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle
VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle Open
Differentiated tissue is particularly vulnerable to alterations in protein and organelle homeostasis. The essential protein VCP, mutated in hereditary inclusion body myopathy, amyotrophic lateral sclerosis and frontotemporal dementia, is c…
View article: AP-SWATH Reveals Direct Involvement of VCP/p97 in Integrated Stress Response Signaling Through Facilitating CReP/PPP1R15B Degradation
AP-SWATH Reveals Direct Involvement of VCP/p97 in Integrated Stress Response Signaling Through Facilitating CReP/PPP1R15B Degradation Open
The ubiquitin-directed AAA-ATPase VCP/p97 facilitates degradation of damaged or misfolded proteins in diverse cellular stress response pathways. Resolving the complexity of its interactions with partner and substrate proteins and understan…