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243 results on '"Clarke, Oliver B."'

1. Structural and molecular basis of choline uptake into the brain by FLVCR2

Author

Cater, Rosemary J., Mukherjee, Dibyanti, Gil-Iturbe, Eva, Erramilli, Satchal K., Chen, Ting, Koo, Katie, Santander, Nicolás, Reckers, Andrew, Kloss, Brian, Gawda, Tomasz, Choy, Brendon C., Zhang, Zhening, Katewa, Aditya, Larpthaveesarp, Amara, Huang, Eric J., Mooney, Scott W. J., Clarke, Oliver B., Yee, Sook Wah, Giacomini, Kathleen M., Kossiakoff, Anthony A., Quick, Matthias, Arnold, Thomas, and Mancia, Filippo

Published
2024
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2. Promiscuous G-protein activation by the calcium-sensing receptor

Author

Zuo, Hao, Park, Jinseo, Frangaj, Aurel, Ye, Jianxiang, Lu, Guanqi, Manning, Jamie J., Asher, Wesley B., Lu, Zhengyuan, Hu, Guo-bin, Wang, Liguo, Mendez, Joshua, Eng, Edward, Zhang, Zhening, Lin, Xin, Grassucci, Robert, Hendrickson, Wayne A., Clarke, Oliver B., Javitch, Jonathan A., Conigrave, Arthur D., and Fan, Qing R.

Published
2024
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3. Structural basis of peptidoglycan synthesis by E. coli RodA-PBP2 complex

Author

Nygaard, Rie, Graham, Chris L. B., Belcher Dufrisne, Meagan, Colburn, Jonathan D., Pepe, Joseph, Hydorn, Molly A., Corradi, Silvia, Brown, Chelsea M., Ashraf, Khuram U., Vickery, Owen N., Briggs, Nicholas S., Deering, John J., Kloss, Brian, Botta, Bruno, Clarke, Oliver B., Columbus, Linda, Dworkin, Jonathan, Stansfeld, Phillip J., Roper, David I., and Mancia, Filippo

Published
2023
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4. Symmetric activation and modulation of the human calcium-sensing receptor

Author

Park, Jinseo, Zuo, Hao, Frangaj, Aurel, Fu, Ziao, Yen, Laura Y., Zhang, Zhening, Mosyak, Lidia, Slavkovich, Vesna N., Liu, Jonathan, Ray, Kimberly M., Cao, Baohua, Vallese, Francesca, Geng, Yong, Chen, Shaoxia, Grassucci, Robert, Dandey, Venkata P., Tan, Yong Zi, Eng, Edward, Lee, Yeji, Kloss, Brian, Liu, Zheng, Hendrickson, Wayne A., Potter, Clinton S., Carragher, Bridget, Graziano, Joseph, Conigrave, Arthur D., Frank, Joachim, Clarke, Oliver B., and Fan, Qing R.

Published
2021

5. Structure of human GABAB receptor in an inactive state

Author

Park, Jinseo, Fu, Ziao, Frangaj, Aurel, Liu, Jonathan, Mosyak, Lidia, Shen, Tong, Slavkovich, Vesna N, Ray, Kimberly M, Taura, Jaume, Cao, Baohua, Geng, Yong, Zuo, Hao, Kou, Yongjun, Grassucci, Robert, Chen, Shaoxia, Liu, Zheng, Lin, Xin, Williams, Justin P, Rice, William J, Eng, Edward T, Huang, Rick K, Soni, Rajesh K, Kloss, Brian, Yu, Zhiheng, Javitch, Jonathan A, Hendrickson, Wayne A, Slesinger, Paul A, Quick, Matthias, Graziano, Joseph, Yu, Hongtao, Fiehn, Oliver, Clarke, Oliver B, Frank, Joachim, and Fan, Qing R

Subjects
Biochemistry and Cell Biology, Biological Sciences, Pain Research, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Calcium, Cryoelectron Microscopy, Ethanolamines, Humans, Ligands, Models, Molecular, Phosphorylcholine, Protein Domains, Protein Multimerization, Protein Subunits, Receptors, GABA-B, Structure-Activity Relationship, General Science & Technology
Abstract

The human GABAB receptor-a member of the class C family of G-protein-coupled receptors (GPCRs)-mediates inhibitory neurotransmission and has been implicated in epilepsy, pain and addiction1. A unique GPCR that is known to require heterodimerization for function2-6, the GABAB receptor has two subunits, GABAB1 and GABAB2, that are structurally homologous but perform distinct and complementary functions. GABAB1 recognizes orthosteric ligands7,8, while GABAB2 couples with G proteins9-14. Each subunit is characterized by an extracellular Venus flytrap (VFT) module, a descending peptide linker, a seven-helix transmembrane domain and a cytoplasmic tail15. Although the VFT heterodimer structure has been resolved16, the structure of the full-length receptor and its transmembrane signalling mechanism remain unknown. Here we present a near full-length structure of the GABAB receptor, captured in an inactive state by cryo-electron microscopy. Our structure reveals several ligands that preassociate with the receptor, including two large endogenous phospholipids that are embedded within the transmembrane domains to maintain receptor integrity and modulate receptor function. We also identify a previously unknown heterodimer interface between transmembrane helices 3 and 5 of both subunits, which serves as a signature of the inactive conformation. A unique 'intersubunit latch' within this transmembrane interface maintains the inactive state, and its disruption leads to constitutive receptor activity.

Published
2020

6. Author Correction: Structure of human GABAB receptor in an inactive state

Author

Park, Jinseo, Fu, Ziao, Frangaj, Aurel, Liu, Jonathan, Mosyak, Lidia, Shen, Tong, Slavkovich, Vesna N, Ray, Kimberly M, Taura, Jaume, Cao, Baohua, Geng, Yong, Zuo, Hao, Kou, Yongjun, Grassucci, Robert, Chen, Shaoxia, Liu, Zheng, Lin, Xin, Williams, Justin P, Rice, William J, Eng, Edward T, Huang, Rick K, Soni, Rajesh K, Kloss, Brian, Yu, Zhiheng, Javitch, Jonathan A, Hendrickson, Wayne A, Slesinger, Paul A, Quick, Matthias, Graziano, Joseph, Yu, Hongtao, Fiehn, Oliver, Clarke, Oliver B, Frank, Joachim, and Fan, Qing R

Subjects
Historical Studies, Biomedical and Clinical Sciences, History, Heritage and Archaeology, General Science & Technology
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

7. Structure of an endosomal signaling GPCR–G protein–β-arrestin megacomplex

Author

Nguyen, Anthony H, Thomsen, Alex RB, Cahill, Thomas J, Huang, Rick, Huang, Li-Yin, Marcink, Tara, Clarke, Oliver B, Heissel, Søren, Masoudi, Ali, Ben-Hail, Danya, Samaan, Fadi, Dandey, Venkata P, Tan, Yong Zi, Hong, Chuan, Mahoney, Jacob P, Triest, Sarah, Little, John, Chen, Xin, Sunahara, Roger, Steyaert, Jan, Molina, Henrik, Yu, Zhiheng, des Georges, Amedee, and Lefkowitz, Robert J

Subjects
Generic health relevance, Animals, Cattle, Cryoelectron Microscopy, Endosomes, GTP-Binding Proteins, Humans, Models, Molecular, Protein Conformation, Receptors, Adrenergic, beta-2, Receptors, G-Protein-Coupled, Receptors, Vasopressin, Signal Transduction, beta-Arrestins, Chemical Sciences, Biological Sciences, Medical and Health Sciences, Biophysics, Developmental Biology
Abstract

Classically, G-protein-coupled receptors (GPCRs) are thought to activate G protein from the plasma membrane and are subsequently desensitized by β-arrestin (β-arr). However, some GPCRs continue to signal through G protein from internalized compartments, mediated by a GPCR-G protein-β-arr 'megaplex'. Nevertheless, the molecular architecture of the megaplex remains unknown. Here, we present its cryo-electron microscopy structure, which shows simultaneous engagement of human G protein and bovine β-arr to the core and phosphorylated tail, respectively, of a single active human chimeric β2-adrenergic receptor with the C-terminal tail of the arginine vasopressin type 2 receptor (β2V2R). All three components adopt their canonical active conformations, suggesting that a single megaplex GPCR is capable of simultaneously activating G protein and β-arr. Our findings provide a structural basis for GPCR-mediated sustained internalized G protein signaling.

Published
2019

9. Structural basis of lipopolysaccharide maturation by the O-antigen ligase

Author

Ashraf, Khuram U., Nygaard, Rie, Vickery, Owen N., Erramilli, Satchal K., Herrera, Carmen M., McConville, Thomas H., Petrou, Vasileios I., Giacometti, Sabrina I., Dufrisne, Meagan Belcher, Nosol, Kamil, Zinkle, Allen P., Graham, Chris L. B., Loukeris, Michael, Kloss, Brian, Skorupinska-Tudek, Karolina, Swiezewska, Ewa, Roper, David I., Clarke, Oliver B., Uhlemann, Anne-Catrin, Kossiakoff, Anthony A., Trent, M. Stephen, Stansfeld, Phillip J., and Mancia, Filippo

Published
2022
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11. Structural determinants of ivabradine block of the open pore of HCN4.

Author

Saponaro, Andrea, Krumbach, Jan H., Chaves-Sanjuan, Antonio, Sharifzadeh, Atiyeh Sadat, Porro, Alessandro, Castelli, Roberta, Hamacher, Kay, Bolognesi, Martino, DiFrancesco, Dario, Clarke, Oliver B., Thiel, Gerhard, and Moroni, Anna

Subjects
IVABRADINE, HYPNOTISM, MOLECULAR dynamics, AMMONIUM ions, HEART cells, DRUG marketing
Abstract

HCN1-4 channels are the molecular determinants of the If/Ih current that crucially regulates cardiac and neuronal cell excitability. HCN dysfunctions lead to sinoatrial block (HCN4), epilepsy (HCN1), and chronic pain (HCN2), widespread medical conditions awaiting subtype-specific treatments. Here, we address the problem by solving the cryo-EM structure of HCN4 in complex with ivabradine, to date the only HCN-specific drug on the market. Our data show ivabradine bound inside the open pore at 3 Å resolution. The structure unambiguously proves that Y507 and I511 on S6 are the molecular determinants of ivabradine binding to the inner cavity, while F510, pointing outside the pore, indirectly contributes to the block by controlling Y507. Cysteine 479, unique to the HCN selectivity filter (SF), accelerates the kinetics of block. Molecular dynamics simulations further reveal that ivabradine blocks the permeating ion inside the SF by electrostatic repulsion, a mechanism previously proposed for quaternary ammonium ions. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Structural and molecular basis of choline uptake into the brain by FLVCR2

Author

Cater, Rosemary J., primary, Mukherjee, Dibyanti, additional, Iturbe, Eva Gil, additional, Erramilli, Satchal K., additional, Chen, Ting, additional, Koo, Katie, additional, Grez, Nicolás Santander, additional, Reckers, Andrew, additional, Kloss, Brian, additional, Gawda, Tomasz, additional, Choy, Brendon C., additional, Zheng, Zhening, additional, Clarke, Oliver B., additional, Yee, Sook Wah, additional, Kossiakoff, Anthony A., additional, Quick, Matthias, additional, Arnold, Thomas, additional, and Mancia, Filippo, additional

Published
2023
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26. Structure of the STRA6 receptor for retinol uptake

Author

Chen, Yunting, Clarke, Oliver B., Kim, Jonathan, Stowe, Sean, Kim, Youn-Kyung, Assur, Zahra, Cavalier, Michael, Godoy-Ruiz, Raquel, von Alpen, Desiree C., Manzini, Chiara, Blaner, William S., Frank, Joachim, Quadro, Loredana, Weber, David J., Shapiro, Lawrence, Hendrickson, Wayne A., and Mancia, Filippo

Published
2016

28. Structural Basis for Gating and Activation of RyR1

Author

Georges, Amédée des, primary, Clarke, Oliver B., additional, Zalk, Ran, additional, Yuan, Qi, additional, Condon, Kendall J., additional, Grassucci, Robert A., additional, Hendrickson, Wayne A., additional, Marks, Andrew R., additional, and Frank, Joachim, additional

Published
2018
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29. Defective Thyroglobulin: Cell Biology of Disease

Author

Zhang, Xiaohan, primary, Young, Crystal, additional, Morishita, Yoshiaki, additional, Kim, Kookjoo, additional, Kabil, Omer O., additional, Clarke, Oliver B., additional, Di Jeso, Bruno, additional, and Arvan, Peter, additional

Published
2022
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30. Mechanism of dual pharmacological correction and potentiation of human CFTR

Author

Wang, Chi, primary, Yang, Zhengrong, additional, Loughlin, Blaine J., additional, Xu, Haijin, additional, Veit, Guido, additional, Vorobiev, Sergey, additional, Clarke, Oliver B., additional, Jiang, Fan, additional, Li, Yaohui, additional, Singh, Shikha, additional, Rich, Zachary, additional, Menten, Elizabeth R., additional, Grassucci, Robert A., additional, Wang, Wei, additional, Mezzell, Allison, additional, Fu, Ziao, additional, Wong, Kam-Ho, additional, Wang, Jing, additional, Wetmore, Diana R., additional, Sutton, R. Bryan, additional, Brouillette, Christie G., additional, Urbatsch, Ina L., additional, Kappes, John C., additional, Lukacs, Gergely L., additional, Frank, Joachim, additional, and Hunt, John F., additional

Published
2022
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35. Structure of a mammalian ryanodine receptor

Author

Zalk, Ran, Clarke, Oliver B., Georges, Amedee des, Grassucci, Robert A., Reiken, Steven, Mancia, Filippo, Hendrickson, Wayne A., Frank, Joachim, and Marks, Andrew R.

Subjects
Ion channels -- Structure, Rabbits -- Physiological aspects, Muscles -- Structure, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Ryanodine receptors (RyRs) mediate the rapid release of calcium ([Ca.sup.2+]) from intracellular stores into the cytosol, which is essential for numerous cellular functions including excitation-contraction coupling in muscle. Lack of sufficient structural detail has impeded understanding of RyR gating and regulation. Here we report the closed-state structure of the 2.3-megadalton complex of the rabbit skeletal muscle type 1 RyR (RyR1), solved by single-particle electron cryomicroscopy at an overall resolution of 4.8 Å. We fitted a polyalanine-level model to all 3,757 ordered residues in each protomer, defining the transmembrane pore in unprecedented detail and placing all cytosolic domains as tertiary folds. The cytosolic assembly is built on an extended α-solenoid scaffold connecting key regulatory domains to the pore. The RyR1 pore architecture places it in the six-transmembrane ion channel superfamily. A unique domain inserted between the second and third transmembrane helices interacts intimately with paired EF-hands originating from the α-solenoid scaffold, suggesting a mechanism for channel gating by [Ca.sup.2+]., Ryanodine receptors (RyRs) are intracellular [Ca.sup.2+] release channels on the sarcoplasmic and endoplasmic reticula required for fundamental cellular functions in most tissues, including skeletal and cardiac muscle excitation-contraction coupling, synaptic [...]

Published
2015
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36. Crystal structure of LGR ligand α2/β5 from Caenorhabditis elegans with implications for the evolution of glycoprotein hormones.

Author

Zhen Gong, Wei Wang, El Omari, Kamel, Lebedev, Andrey A., Clarke, Oliver B., and Hendrickson, Wayne A.

Subjects
GLYCOPROTEIN hormones, CAENORHABDITIS elegans, CRYSTAL structure, MOLECULAR evolution, FOLLICLE-stimulating hormone, EXCHANGE
Abstract

A family of leucine-rich-repeat-containing G-protein-coupled receptors (LGRs) mediate diverse physiological responses when complexed with their cognate ligands. LGRs are present in all metazoan animals. In humans, the LGR ligands include glycoprotein hormones (GPHs) chorionic gonadotropin (hCG), luteinizing hormone, follicle-stimulating hormone (hFSH), and thyroid-stimulating hormone (hTSH). These hormones are aß heterodimers of cystine-knot protein chains. LGRs and their ligand chains have coevolved. Ancestral hormone homologs, present in both bilaterian animals and chordates, are identified as a2ß5. We have used single-wavelength anomalous diffraction and molecular replacement to determine structures of the a2ß5 hormone from Caenorhabditis elegans (Cea2ß5). Cea2ß5 is unglycosylated, as are many other a2ß5 hormones. Both Hsa2ß5, the human homolog of Cea2ß5, and hTSH activate the same receptor (hTSHR). Despite having little sequence similarity to vertebrate GPHs, apart from the cysteine patterns from core disulfide bridges, Cea2ß5 is generally similar in structure to these counterparts; however, its a2 and ß5 subunits are more symmetric as compared with a and ß of hCG and hFSH. This quasisymmetry suggests a hypothetical homodimeric antecedent of the a2ß5 and aß heterodimers. Known structures together with AlphaFold models from the sequences for other LGR ligands provide representatives for the molecular evolution of LGR ligands from early metazoans through the present-day GPHs. The experimental Cea2ß5 structure validates its AlphaFold model, and thus also that for Hsa2ß5; and interfacial characteristics in a model for the Hsa2ß5:hTSHR complex are similar to those found in an experimental hTSH:hTSHR structure. [ABSTRACT FROM AUTHOR]

Published
2023
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41. Physiologically relevant free Ca(2+) ion concentrations regulate STRA6-calmodulin complex formation via the BP2 region of STRA6: Calcium regulation of the calmodulin-STRA6 complex

Author

Young, Brianna D., Varney, Kristen M., Wilder, Paul T., Costabile, Brianna K., Pozharski, Edwin, Cook, Mary E., Godoy-Ruiz, Raquel, Clarke, Oliver B., Mancia, Filippo, and Weber, David J.

Subjects
Magnetic Resonance Spectroscopy, Protein Conformation, Membrane Transport Proteins, Zebrafish Proteins, Article, Peptide Fragments, Recombinant Proteins, Spectrometry, Fluorescence, Calmodulin, Multiprotein Complexes, Humans, Thermodynamics, Calcium, EF Hand Motifs, Vitamin A
Abstract

The interaction of calmodulin (CaM) with the receptor for retinol uptake, STRA6, involves an α-helix termed BP2 that is located on the intracellular side of this homodimeric transporter [1]. In the absence of Ca(2+), NMR data showed that a peptide derived from BP2 bound to the C-terminal lobe (C-lobe) of Mg(2+)-bound CaM ((Mg)CaM). Upon titration of Ca(2+) into (Mg)CaM-BP2, NMR chemical shift perturbations (CSPs) were observed for residues in the C-lobe, including those in the EF-hand Ca(2+)-binding domains, EF3 and EF4 ((Ca)K(D) = 60 ± 7 nM). As higher concentrations of free Ca(2+) were achieved, CSPs occurred for residues in the N-terminal lobe (N-lobe) including those in EF1 and EF2 ((Ca)K(D) = 1,000 ± 160 nM). Thermodynamic and kinetic Ca(2+) binding studies showed that BP2 addition increased the Ca(2+)-binding affinity of CaM and slowed its Ca(2+) dissociation rates (k(off)) in both the C- and N-lobe EF-hand domains, respectively. These data are consistent with BP2 binding to the C-lobe of CaM at low free Ca(2+) concentrations (

Published
2021

43. Ion currents through Kir potassium channels are gated by anionic lipids

Author

Jin, Ruitao, primary, He, Sitong, additional, Black, Katrina A., additional, Clarke, Oliver B., additional, Wu, Di, additional, Bolla, Jani R., additional, Johnson, Paul, additional, Periasamy, Agalya, additional, Wardak, Ahmad, additional, Czabotar, Peter, additional, Colman, Peter M., additional, Robinson, Carol V., additional, Laver, Derek, additional, Smith, Brian J., additional, and Gulbis, Jacqueline M., additional

Published
2021
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46. Gating movements and ion permeation in HCN4 pacemaker channels

Author

Saponaro, Andrea, primary, Bauer, Daniel, additional, Giese, M. Hunter, additional, Swuec, Paolo, additional, Porro, Alessandro, additional, Gasparri, Federica, additional, Sharifzadeh, Atiyeh Sadat, additional, Chaves-Sanjuan, Antonio, additional, Alberio, Laura, additional, Parisi, Giacomo, additional, Cerutti, Gabriele, additional, Clarke, Oliver B., additional, Hamacher, Kay, additional, Colecraft, Henry M., additional, Mancia, Filippo, additional, Hendrickson, Wayne A., additional, Siegelbaum, Steven A., additional, DiFrancesco, Dario, additional, Bolognesi, Martino, additional, Thiel, Gerhard, additional, Santoro, Bina, additional, and Moroni, Anna, additional

Published
2021
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47. Additional file 1 of RyR1-related myopathy mutations in ATP and calcium binding sites impair channel regulation

Author

Yuan, Qi, Dridi, Haikel, Clarke, Oliver B., Reiken, Steven, Melville, Zephan, Wronska, Anetta, Kushnir, Alexander, Zalk, Ran, Sittenfeld, Leah, and Marks, Andrew R.

Subjects
musculoskeletal system, tissues
Abstract

Additional file 1: Figure 1. RyR1-S4028L patient mutation causes RyR1 channel leak. (A) The mutant RyR1-S4028L channel was PKA phosphorylated at Ser2844 and oxidized (DNP) compared to control. PP1 and DTT were used to reverse the oxidation and phosphorylation. (B) The mutant RyR1-S4028L channels exhibited increased sensitivity to Ca2+-dependent activation consistent with channel leak as determined by 3[H]-ryanodine binding at the indicated [Ca2+]cyt. Data are presented as mean �� S.E.M from 4 for each group *P < 0.05 vs. WT; #P < 0.05 vs. RyR1-S4028L, ANOVA, Tukey-Kramer with post hoc correction.

Published
2021
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