Gergely L. Lukács
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View article: Substrate recognition by the human mitochondrial processing peptidase and its processing of PINK1
Substrate recognition by the human mitochondrial processing peptidase and its processing of PINK1 Open
Nuclear-encoded mitochondrial proteins rely on N-terminal targeting sequences (N-MTS) for their import. Most N-MTSs are cleaved in the matrix by the mitochondrial processing peptidase (MPP), a heterodimeric metalloprotease composed of (α) …
View article: Substrate recognition by the human mitochondrial processing peptidase and its processing of PINK1
Substrate recognition by the human mitochondrial processing peptidase and its processing of PINK1 Open
Nuclear-encoded mitochondrial proteins rely on N-terminal targeting sequences (N-MTS) for their import. These N-MTSs interact with the translocation machinery and are cleaved in the matrix by the mitochondrial processing peptidase (MPP), a…
View article: SARS-CoV-2 envelope protein alters calcium signaling via SERCA interactions
SARS-CoV-2 envelope protein alters calcium signaling via SERCA interactions Open
The clinical management of severe COVID-19 cases is not yet well resolved. Therefore, it is important to identify and characterize cell signaling pathways involved in virus pathogenesis that can be targeted therapeutically. Envelope (E) pr…
View article: Synthesis and Biological Evaluation of Pyrazole–Pyrimidones as a New Class of Correctors of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
Synthesis and Biological Evaluation of Pyrazole–Pyrimidones as a New Class of Correctors of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Open
Cystic fibrosis (CF) is caused by the functional expression defect of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Despite the recent success in CFTR modulator development, the available correctors only partially…
View article: Analysis of AlphaMissense data in different protein groups and structural context
Analysis of AlphaMissense data in different protein groups and structural context Open
View article: HERC3 facilitates ERAD of select membrane proteins by recognizing membrane-spanning domains
HERC3 facilitates ERAD of select membrane proteins by recognizing membrane-spanning domains Open
Aberrant proteins located in the endoplasmic reticulum (ER) undergo rapid ubiquitination by multiple ubiquitin (Ub) E3 ligases and are retrotranslocated to the cytosol as part of the ER-associated degradation (ERAD). Despite several ERAD b…
View article: Readthrough-induced misincorporated amino acid ratios guide mutant-specific therapeutic approaches for two CFTR nonsense mutations
Readthrough-induced misincorporated amino acid ratios guide mutant-specific therapeutic approaches for two CFTR nonsense mutations Open
Cystic fibrosis (CF) is a monogenic disease caused by mutations in the CF transmembrane conductance regulator ( CFTR ) gene. Premature termination codons (PTCs) represent ∼9% of CF mutations that typically cause severe expression defects o…
View article: Lightway access to AlphaMissense data that demonstrates a balanced performance of this missense mutation predictor
Lightway access to AlphaMissense data that demonstrates a balanced performance of this missense mutation predictor Open
Single amino acid substitutions can profoundly affect protein folding, dynamics, and function, leading to potential pathological consequences. The ability to discern between benign and pathogenic substitutions is pivotal for therapeutic in…
View article: Folding correctors can restore CFTR posttranslational folding landscape by allosteric domain–domain coupling
Folding correctors can restore CFTR posttranslational folding landscape by allosteric domain–domain coupling Open
View article: Folding correctors can restore CFTR posttranslational folding landscape by allosteric domain-domain coupling
Folding correctors can restore CFTR posttranslational folding landscape by allosteric domain-domain coupling Open
The folding/misfolding and pharmacological rescue of multidomain ATP-binding cassette (ABC) C-subfamily transporters, essential for organismal health, remain incompletely understood. The ABCC transporters core consists of two nucleotide bi…
View article: HERC3 E3 ligase provides an ERAD branch eliminating select membrane proteins
HERC3 E3 ligase provides an ERAD branch eliminating select membrane proteins Open
Aberrant proteins located in the endoplasmic reticulum (ER) undergo rapid ubiquitination by multiple ubiquitin (Ub) E3 ligases and are retrotranslocated to the cytosol as part of the ER-associated degradation (ERAD). Despite several ERAD b…
View article: 335 Cryogenic electron microscopy studies of human CFTR folding and conformational dynamics elucidate a novel potentiator binding site in the nucleotide binding domains that supports an alternative channelgating mechanism
335 Cryogenic electron microscopy studies of human CFTR folding and conformational dynamics elucidate a novel potentiator binding site in the nucleotide binding domains that supports an alternative channelgating mechanism Open
View article: SARS-CoV-2 Envelope protein alters calcium signaling via SERCA interactions
SARS-CoV-2 Envelope protein alters calcium signaling via SERCA interactions Open
The clinical management of severe COVID-19 cases is not yet well resolved. Therefore, it is important to identify and characterize cell signaling pathways involved in virus pathogenesis that can be targeted therapeutically. Envelope (E) pr…
View article: Mechanism of dual pharmacological correction and potentiation of human CFTR
Mechanism of dual pharmacological correction and potentiation of human CFTR Open
Cystic fibrosis (CF) is caused by mutations in a chloride channel called the human Cystic Fibrosis Transmembrane Conductance Regulator (hCFTR). We used cryo-EM global conformational ensemble reconstruction to characterize the mechanism by …
View article: Keratin 8 is a scaffolding and regulatory protein of ERAD complexes
Keratin 8 is a scaffolding and regulatory protein of ERAD complexes Open
View article: Measuring EGFR plasma membrane density, stability, internalization, and recycling in alive adherent cells by cell surface ELISA
Measuring EGFR plasma membrane density, stability, internalization, and recycling in alive adherent cells by cell surface ELISA Open
View article: A PI3Kγ mimetic peptide triggers CFTR gating, bronchodilation, and reduced inflammation in obstructive airway diseases
A PI3Kγ mimetic peptide triggers CFTR gating, bronchodilation, and reduced inflammation in obstructive airway diseases Open
Cyclic adenosine 3′,5′-monophosphate (cAMP)–elevating agents, such as β 2 -adrenergic receptor (β 2 -AR) agonists and phosphodiesterase (PDE) inhibitors, remain a mainstay in the treatment of obstructive respiratory diseases, conditions ch…
View article: Ubr1-induced selective endophagy/autophagy protects against the endosomal and Ca2+-induced proteostasis disease stress
Ubr1-induced selective endophagy/autophagy protects against the endosomal and Ca2+-induced proteostasis disease stress Open
View article: Keratin 8 is a scaffolding and regulatory protein of ERAD complexes
Keratin 8 is a scaffolding and regulatory protein of ERAD complexes Open
Early recognition and enhanced degradation of misfolded proteins by the endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD) cause defective protein secretion and membrane targeting, as exemplified for Z-alpha 1 …
View article: Nanomechanics combined with HDX reveals allosteric drug binding sites of CFTR NBD1
Nanomechanics combined with HDX reveals allosteric drug binding sites of CFTR NBD1 Open
View article: Ins and outs of AlphaFold2 transmembrane protein structure predictions
Ins and outs of AlphaFold2 transmembrane protein structure predictions Open
View article: Mechanism of PINK1 activation by autophosphorylation and insights into assembly on the TOM complex
Mechanism of PINK1 activation by autophosphorylation and insights into assembly on the TOM complex Open
View article: 622: CFTR protein production core: Availability of purified full-length wild-type and disease-mutant CFTR proteins and new experimental data revealing insights into CFTR function and disease mechanism
622: CFTR protein production core: Availability of purified full-length wild-type and disease-mutant CFTR proteins and new experimental data revealing insights into CFTR function and disease mechanism Open
View article: 625: Optimized modulator combinations for rare CFTR mutants with good responsiveness to single correctors
625: Optimized modulator combinations for rare CFTR mutants with good responsiveness to single correctors Open
View article: Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes
Endofin is required for HD-PTP and ESCRT-0 interdependent endosomal sorting of ubiquitinated transmembrane cargoes Open
Internalized and ubiquitinated signaling receptors are silenced by their intraluminal budding into multivesicular bodies aided by the endosomal sorting complexes required for transport (ESCRT) machinery. HD-PTP, an ESCRT protein, forms com…
View article: Ubr1-induced selective endo-phagy/autophagy protects against the endosomal and Ca<sup>2+</sup>-induced proteostasis disease stress
Ubr1-induced selective endo-phagy/autophagy protects against the endosomal and Ca<sup>2+</sup>-induced proteostasis disease stress Open
The defence mechanisms against endo-lysosomal homeostasis stress remain incompletely understood. Here, we identify Ubr1 as a protein quality control (QC) ubiquitin ligase that counteracts proteostasis stress by enhancing cargo selective au…
View article: Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations
Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations Open
View article: AlphaFold2 transmembrane protein structure prediction shines
AlphaFold2 transmembrane protein structure prediction shines Open
Transmembrane (TM) proteins are major drug targets, indicated by the high percentage of prescription drugs acting on them. For a rational drug design and an understanding of mutational effects on protein function, structural data at atomic…
View article: Nanomechanics combined with HDX reveal allosteric drug binding sites of CFTR NBD1
Nanomechanics combined with HDX reveal allosteric drug binding sites of CFTR NBD1 Open
Cystic fibrosis is most frequently caused by the deletion of F508 (ΔF508) in CFTR’s nucleotide binding domain 1 (NBD1), compromising CFTR folding, stability and domain assembly. The limitation of developing a successful therapy is due to t…
View article: Structure of PINK1 reveals autophosphorylation dimer and provides insights into binding to the TOM complex
Structure of PINK1 reveals autophosphorylation dimer and provides insights into binding to the TOM complex Open
Summary Mutations in PINK1 causes autosomal-recessive Parkinson’s disease. Mitochondrial damage results in PINK1 import arrest on the Translocase of the Outer Mitochondrial Membrane (TOM) complex, resulting in the activation of its ubiquit…