Alberto J. Gonzalez-Hernandez
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View article: Structural Diversity and Dynamics of Metabotropic Glutamate Receptor/Beta-Arrestin Coupling
Structural Diversity and Dynamics of Metabotropic Glutamate Receptor/Beta-Arrestin Coupling Open
Beta-arrestins (β-arrs) are cytosolic proteins which mediate G protein-coupled receptor (GPCR) desensitization, endocytosis, and signaling. Despite the widespread physiological roles of β-arr coupling, the molecular basis of GPCR/β-arr int…
View article: Control of G protein–coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains
Control of G protein–coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains Open
G protein–coupled receptors (GPCRs) control intracellular signaling cascades via agonist-dependent coupling to intracellular transducers including heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. In addition to their critical…
View article: Deuteration as a General Strategy to Enhance Azobenzene‐Based Photopharmacology
Deuteration as a General Strategy to Enhance Azobenzene‐Based Photopharmacology Open
Chemical photoswitches have become a widely used approach for the remote control of biological functions with spatiotemporal precision. Several molecular scaffolds have been implemented to improve photoswitch characteristics, ranging from …
View article: Deuteration as a General Strategy to Enhance Azobenzene‐Based Photopharmacology
Deuteration as a General Strategy to Enhance Azobenzene‐Based Photopharmacology Open
Chemical photoswitches have become a widely used approach for the remote control of biological functions with spatiotemporal precision. Several molecular scaffolds have been implemented to improve photoswitch characteristics, ranging from …
View article: A general method for near-infrared photoswitching in biology, demonstrated by the >700 nm photocontrol of GPCR activity in brain slices
A general method for near-infrared photoswitching in biology, demonstrated by the >700 nm photocontrol of GPCR activity in brain slices Open
Azobenzene molecular switches are widely used to photocontrol material properties, and biological activity in cell culture, via photoisomerisation between E and Z isomers. However, because population photoswitching is incomplete, their dyn…
View article: An epigenetic barrier sets the timing of human neuronal maturation
An epigenetic barrier sets the timing of human neuronal maturation Open
The pace of human brain development is highly protracted compared with most other species 1–7 . The maturation of cortical neurons is particularly slow, taking months to years to develop adult functions 3–5 . Remarkably, such protracted ti…
View article: Distinct beta-arrestin coupling and intracellular trafficking of metabotropic glutamate receptor homo- and heterodimers
Distinct beta-arrestin coupling and intracellular trafficking of metabotropic glutamate receptor homo- and heterodimers Open
The metabotropic glutamate receptors (mGluRs) are family C, dimeric G protein–coupled receptors (GPCRs), which play critical roles in synaptic transmission. Despite an increasing appreciation of the molecular diversity of this family, how …
View article: Deuteration provides a general strategy to enhance azobenzene-based photopharmacology
Deuteration provides a general strategy to enhance azobenzene-based photopharmacology Open
Herein, we present deuterated azobenzene photoswitches as a general means of enhancing photopharmacological molecules. Deuteration can improve azobenzene performance in terms of light sensitivity, photoswitch efficiency, and photoswitch ki…
View article: FRI162 Ligand-dependent Photocrosslinking of Mineralocorticoid Receptors Using Site-directed Incorporation of Unnatural Amino Acids
FRI162 Ligand-dependent Photocrosslinking of Mineralocorticoid Receptors Using Site-directed Incorporation of Unnatural Amino Acids Open
Disclosure: B. Almeida-Prieto: None. A.J. Gonzalez-Hernandez: None. T. Giraldez: None. D. Alvarez de la Rosa: None. Steroid receptors dimerize prior DNA binding as a key step for translational activation of target genes. It appears that se…
View article: Azobenzenes can achieve near-infrared photocontrol in biological systems, with quantitative Z→E photoisomerization, via singlet manifold photoredox
Azobenzenes can achieve near-infrared photocontrol in biological systems, with quantitative Z→E photoisomerization, via singlet manifold photoredox Open
Here we develop a high-performance approach to photoswitching, by exploiting singlet manifold photoredox between azobenzenes and covalently attached auxiliary chromophores. This enables well-penetrating red/NIR light of 630-740 nm, to whic…
View article: Control of G protein-coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains
Control of G protein-coupled receptor function via membrane-interacting intrinsically disordered C-terminal domains Open
G protein-coupled receptors (GPCRs) control intracellular signaling cascades via agonist-dependent coupling to intracellular transducers including heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. In addition to their critical…
View article: Structural basis of allosteric modulation of metabotropic glutamate receptor activation and desensitization
Structural basis of allosteric modulation of metabotropic glutamate receptor activation and desensitization Open
The metabotropic glutamate receptors (mGluRs) are neuromodulatory family C G protein coupled receptors which assemble as dimers and allosterically couple extracellular ligand binding domains (LBDs) to transmembrane domains (TMDs) to drive …
View article: State-dependent photocrosslinking unveiled the role of intersubunit interfaces on Ca<sup>2+</sup>activating mechanisms of the BK channel
State-dependent photocrosslinking unveiled the role of intersubunit interfaces on Ca<sup>2+</sup>activating mechanisms of the BK channel Open
BK channels are high-conductance potassium channels that are activated by voltage and Ca 2+ . The pore-forming α-subunits form homotetramers including a membrane-spanning domain and a cytosolic domain with a tandem of RCK-like domains (RCK…
View article: Profiling the proximal proteome of the mu opioid receptor identifies novel regulators of receptor signaling and trafficking
Profiling the proximal proteome of the mu opioid receptor identifies novel regulators of receptor signaling and trafficking Open
The mu opioid receptor (μOR), a prototypic member of the large G protein-coupled receptor (GPCR) family, represents an important target of therapeutic and abused drugs. To date, most of our understanding of μOR activity has focused on sign…
View article: NMDA receptor–BK channel coupling regulates synaptic plasticity in the barrel cortex
NMDA receptor–BK channel coupling regulates synaptic plasticity in the barrel cortex Open
Significance N -methyl-D-aspartate (NMDA) receptors are critical triggers for neuronal plasticity. We show that large-conductance Ca 2+ - and voltage-gated K + (BK) channels serve as feedback regulators of NMDA receptor–mediated calcium in…
View article: NMDA receptor–BK channel coupling regulates synaptic plasticity in the barrel cortex
NMDA receptor–BK channel coupling regulates synaptic plasticity in the barrel cortex Open
SUMMARY Postsynaptic N-methyl-D-aspartate receptors (NMDARs) are crucial mediators of synaptic plasticity due to their ability to act as coincidence detectors of presynaptic and postsynaptic neuronal activity. However, NMDARs exist within …
View article: Cereblon Regulates BK Channel Expression at Presynaptic and Postsynaptic Sites in Excitatory Synapses
Cereblon Regulates BK Channel Expression at Presynaptic and Postsynaptic Sites in Excitatory Synapses Open
Cereblon is a substrate receptor protein for the CRL4A E3 ubiquitin ligase complex. As such, cereblon binds to different proteins to promote their ubiquitination and degradation ([Zheng and Shabek, 2017][1]). Cereblon is highly expressed i…
View article: Physiological Roles and Therapeutic Potential of Ca2+ Activated Potassium Channels in the Nervous System
Physiological Roles and Therapeutic Potential of Ca2+ Activated Potassium Channels in the Nervous System Open
Within the potassium ion channel family, calcium activated potassium (KCa) channels are unique in their ability to couple intracellular Ca2+ signals to membrane potential variations. KCa channels are diversely distributed throughout the ce…