The overall goal of this project is to examine, at a molecular level, the correlation between structure and function for several neurotransmitter-gated channels, receptors, and related proteins. Currently, the main focus of the laboratory is the examination of the secondary structure, topology, and functional role of domains and specific residues of the homomeric recombinant human $alph$1 glycine receptor overexpressed in a baculovirus expression system. This inhibitory gated anionic channel is a member of the ligand-gated superfamily, which include the homologous nicotinic acetylcholine receptor, the 5-HT3 serotonin receptor, and the GABA receptor, all of which act in rapid mediation of signal transduction at the synapse. These investigations may provide insight into the general conserved mechanism used in channel design. Analogous studies concerning the NMDA type glumatmate receptors and the gonadotropin releasing hormones (GnRH) receptor will also be conducted. These receptors, too, are members of large families, and may their structural featur may be paradigmatic; the NMDA receptor is a member of the excitatory glutamate receptor family which act in synaptic transmission and excitotoxicity, and the GnRH receptor is a member of the large G protein coupled receptors and is a pivotal role in regulating coordination of the neural and endocrine systems. In addition, crystalliszation trails of EP 24.15 a zinc metalloendopeptidase which degrades GnRH, are also underway.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR006009-10
Application #
6221066
Study Section
Project Start
1999-08-01
Project End
2000-07-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
10
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Mellon Pitts Corporation (Mpc Corp)
Department
Type
DUNS #
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Simakov, Nikolay A; Kurnikova, Maria G (2018) Membrane Position Dependency of the pKa and Conductivity of the Protein Ion Channel. J Membr Biol 251:393-404
Yonkunas, Michael; Buddhadev, Maiti; Flores Canales, Jose C et al. (2017) Configurational Preference of the Glutamate Receptor Ligand Binding Domain Dimers. Biophys J 112:2291-2300
Hwang, Wonmuk; Lang, Matthew J; Karplus, Martin (2017) Kinesin motility is driven by subdomain dynamics. Elife 6:
Earley, Lauriel F; Powers, John M; Adachi, Kei et al. (2017) Adeno-associated Virus (AAV) Assembly-Activating Protein Is Not an Essential Requirement for Capsid Assembly of AAV Serotypes 4, 5, and 11. J Virol 91:
Subramanian, Sandeep; Chaparala, Srilakshmi; Avali, Viji et al. (2016) A pilot study on the prevalence of DNA palindromes in breast cancer genomes. BMC Med Genomics 9:73
Ramakrishnan, N; Tourdot, Richard W; Radhakrishnan, Ravi (2016) Thermodynamic free energy methods to investigate shape transitions in bilayer membranes. Int J Adv Eng Sci Appl Math 8:88-100
Zhang, Yimeng; Li, Xiong; Samonds, Jason M et al. (2016) Relating functional connectivity in V1 neural circuits and 3D natural scenes using Boltzmann machines. Vision Res 120:121-31
Lee, Wei-Chung Allen; Bonin, Vincent; Reed, Michael et al. (2016) Anatomy and function of an excitatory network in the visual cortex. Nature 532:370-4
Murty, Vishnu P; Calabro, Finnegan; Luna, Beatriz (2016) The role of experience in adolescent cognitive development: Integration of executive, memory, and mesolimbic systems. Neurosci Biobehav Rev 70:46-58
Shafee, Rebecca; Buckner, Randy L; Fischl, Bruce (2015) Gray matter myelination of 1555 human brains using partial volume corrected MRI images. Neuroimage 105:473-85

Showing the most recent 10 out of 292 publications