Structural biology of membrane protein complexes: Glutamate Receptors and beyond
In our group we are interested in the understanding the molecular mechanisms of membrane proteins. Currently we are working on Glutamate Receptors, ligand gated ion channels involved in neurotransmission and memory formation
Funding
"Ramón y Cajal" program (Fondo Social Europeo, Agencia Española de Investigación). RYC2018-025720-I
"Proyectos I+D+I" (Agencia Española de Investigación) PI of PID2019-106284GA-I00
"Proyectos Generación de conocimiento" (Agencia Estatal de investigación") PID2022-140185NB-I00
Cryo-EM of membrane protein complexes
Characterization of protein dynamics
Effect of lipids in membrane protein structure and function
Membrane proteins as drug targets
Publications
2022
Herguedas B*, Kohegyi BK*, Dohrke JN, Watson JF, Zhang D, Ho H, Shaikh SA, Lape R, Krieger JM, Greger IH. Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nat Commun. 2022 Feb 8;13(1):734. doi: 10.1038/s41467-022-28404-7.PMID: 35136046
2019
Herguedas B*, Watson JF, Ho H, Cais O, García-Nafría J, Greger IH*. Architecture of the heteromeric GluA1/2 AMPA receptor in complex with the auxiliary subunit TARP γ8. Science. 2019 Apr 26;364(6438):eaav9011. doi: 10.1126/science.aav9011. Epub 2019 Mar 14 PMID: 30872532 *corresponding author
Lee JY*, Krieger J*, Herguedas B*, García-Nafría J*, Dutta A, Shaikh SA, Greger IH, Bahar I. Druggability Simulations and X-Ray Crystallography Reveal a Ligand-Binding Site in the GluA3 AMPA Receptor N-Terminal Domain. Structure. 2019 Feb 5;27(2):241-252.e3. doi: 10.1016/j.str.2018.10.017. Epub 2018 Dec 6. PMID: 30528594 Free PMC article. *co-first authors
2017
Serrano A, Sebastián M, Arilla-Luna S, Baquedano S, Herguedas B, Velázquez-Campoy A, Martínez-Júlvez M, Medina M. The trimer interface in the quaternary structure of the bifunctional prokaryotic FAD synthetase from Corynebacterium ammoniagenes. Sci Rep. 2017 Mar 24;7(1):404. doi: 10.1038/s41598-017-00402-6.PMID: 28341845
2016
García-Nafría J, Herguedas B, Watson JF, Greger IH.The dynamic AMPA receptor extracellular region: a platform for synaptic protein interactions. J Physiol. 2016 Oct 1;594(19):5449-58. doi: 10.1113/JP271844. Epub 2016 Apr 29. PMID: 26891027 Free PMC article. Review.
Herguedas B*, García-Nafría J*, Cais O, Fernández-Leiro R, Krieger J, Ho H, Greger IH. Structure and organization of heteromeric AMPA-type glutamate receptors. Science. 2016 Apr 29;352(6285):aad3873. doi: 10.1126/science.aad3873. Epub 2016 Mar 10. PMID: 26966189 Free PMC article. *co-first authors
2015
Herguedas B, Lans I, Sebastián M, Hermoso JA, Martínez-Júlvez M, Medina M. Structural insights into the synthesis of FMN in prokaryotic organisms. Acta Crystallogr D Biol Crystallogr. 2015 Dec 1;71(Pt 12):2526-42. doi: 10.1107/S1399004715019641. Epub 2015 Nov 27. PMID: 26627660
Serrano A, Sebastián M, Arilla-Luna S, Baquedano S, Pallarés MC, Lostao A, Herguedas B, Velázquez-Campoy A, Martínez-Júlvez M, Medina M. Quaternary organization in a bifunctional prokaryotic FAD synthetase: Involvement of an arginine at its adenylyltransferase module on the riboflavin kinase activity. Biochim Biophys Acta. 2015 Aug;1854(8):897-906. doi: 10.1016/j.bbapap.2015.03.005. Epub 2015 Mar 21. PMID: 25801930
Ferreira P, Hernández-Ortega A, Lucas F, Carro J, Herguedas B, Borrelli KW, Guallar V, Martínez AT, Medina M. Aromatic stacking interactions govern catalysis in aryl-alcohol oxidase. FEBS J. 2015 Aug;282(16):3091-106. doi: 10.1111/febs.13221. Epub 2015 Feb 23. PMID: 25639975 Free article.
2014
Cais O, Herguedas B, Krol K, Cull-Candy SG, Farrant M, Greger IH. Mapping the interaction sites between AMPA receptors and TARPs reveals a role for the receptor N-terminal domain in channel gating. Cell Rep. 2014 Oct 23;9(2):728-40. doi: 10.1016/j.celrep.2014.09.029. Epub 2014 Oct 16.
Ferreira P, Villanueva R, Martínez-Júlvez M, Herguedas B, Marcuello C, Fernandez-Silva P, Cabon L, Hermoso JA, Lostao A, Susin SA, Medina M Structural insights into the coenzyme mediated monomer-dimer transition of the pro-apoptotic apoptosis inducing factor. Biochemistry. 2014 Jul 1;53(25):4204-15. doi: 10.1021/bi500343r. Epub 2014 Jun 20. PMID: 24914854
2013
Sánchez-Azqueta A, Herguedas B, Hurtado-Guerrero R, Hervás M, Navarro JA, Martínez-Júlvez M, Medina M. A hydrogen bond network in the active site of Anabaena ferredoxin-NADP(+) reductase modulates its catalytic efficiency. Biochim Biophys Acta. 2014 Feb;1837(2):251-63. doi: 10.1016/j.bbabio.2013.10.010. Epub 2013 Nov 4. PMID: 24200908
Herguedas B, Krieger J, Greger IH. Receptor heteromeric assembly-how it works and why it matters: the case of ionotropic glutamate receptors. Prog Mol Biol Transl Sci. 2013;117:361-86. doi: 10.1016/B978-0-12-386931-9.00013-1. PMID: 23663975 Review.
Serrano A, Frago S, Herguedas B, Martínez-Júlvez M, Velázquez-Campoy A, Medina M. Key residues at the riboflavin kinase catalytic site of the bifunctional riboflavin kinase/FMN adenylyltransferase from Corynebacterium ammoniagenes. Cell Biochem Biophys. 2013 Jan;65(1):57-68. doi: 10.1007/s12013-012-9403-9. PMID: 22892871
2010
Peregrina JR, Sánchez-Azqueta A, Herguedas B, Martínez-Júlvez M, Medina M. Role of specific residues in coenzyme binding, charge-transfer complex formation, and catalysis in Anabaena ferredoxin NADP+-reductase. Biochim Biophys Acta. 2010 Sep;1797(9):1638-46. doi: 10.1016/j.bbabio.2010.05.006. Epub 2010 May 21. PMID: 20471952
Herguedas B, Martínez-Júlvez M, Frago S, Medina M, Hermoso JA. Oligomeric state in the crystal structure of modular FAD synthetase provides insights into its sequential catalysis in prokaryotes. J Mol Biol. 2010 Jul 9;400(2):218-30. doi: 10.1016/j.jmb.2010.05.018. Epub 2010 May 13. PMID: 20471397
Ferreira P, Hernández-Ortega A, Herguedas B, Rencoret J, Gutiérrez A, Martínez MJ, Jiménez-Barbero J, Medina M, Martínez AT. Kinetic and chemical characterization of aldehyde oxidation by fungal aryl-alcohol oxidase. Biochem J. 2010 Jan 15;425(3):585-93. doi: 10.1042/BJ20091499. PMID: 19891608
2009
Herguedas B, Martínez-Júlvez M, Frago S, Medina M, Hermoso JA. Crystallization and preliminary X-ray diffraction studies of FAD synthetase from Corynebacterium ammoniagenes. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009 Dec 1;65(Pt 12):1285-8. doi: 10.1107/S1744309109044789. Epub 2009 Nov 27. PMID: 20054130 Free PMC article.
Ferreira P, Hernandez-Ortega A, Herguedas B, Martínez AT, Medina M. Aryl-alcohol oxidase involved in lignin degradation: a mechanistic study based on steady and pre-steady state kinetics and primary and solvent isotope effects with two alcohol substrates. J Biol Chem. 2009 Sep 11;284(37):24840-7. doi: 10.1074/jbc.M109.011593. Epub 2009 Jul 2. PMID: 19574215 Free PMC article.
Peregrina JR, Herguedas B, Hermoso JA, Martínez-Júlvez M, Medina M. Protein motifs involved in coenzyme interaction and enzymatic efficiency in anabaena ferredoxin-NADP+ reductase. Biochemistry. 2009 Apr 14;48(14):3109-19. doi: 10.1021/bi802077c. PMID: 19219975
2008
Goñi G, Herguedas B, Hervás M, Peregrina JR, De la Rosa MA, Gómez-Moreno C, Navarro JA, Hermoso JA, Martínez-Júlvez M, Medina M. Flavodoxin: a compromise between efficiency and versatility in the electron transfer from Photosystem I to Ferredoxin-NADP(+) reductase. Biochim Biophys Acta. 2009 Mar;1787(3):144-54. doi: 10.1016/j.bbabio.2008.12.006. Epub 2008 Dec 24. PMID: 19150326
2007
Frago S, Goñi G, Herguedas B, Peregrina JR, Serrano A, Perez-Dorado I, Molina R, Gómez-Moreno C, Hermoso JA, Martínez-Júlvez M, Mayhew SG, Medina M. Tuning of the FMN binding and oxido-reduction properties by neighboring side chains in Anabaena flavodoxin. Arch Biochem Biophys. 2007 Nov 15;467(2):206-17. doi: 10.1016/j.abb.2007.08.024. Epub 2007 Aug 29. PMID: 17904516
Carpena X, Wiseman B, Deemagarn T, Herguedas B, Ivancich A, Singh R, Loewen PC, Fita I. Roles for Arg426 and Trp111 in the modulation of NADH oxidase activity of the catalase-peroxidase KatG from Burkholderia pseudomallei inferred from pH-induced structural changes. Biochemistry. 2006 Apr 25;45(16):5171-9. doi: 10.1021/bi060017f. PMID: 16618106