Difference: FredNaider (4 vs. 5)

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Public grant information (from Crisp)

Grant Number: 2R01GM022087-31A2 Project Title: Peptide-Cell Interactions in Saccharomyces cerevisiae PI Information: Name Email Title BECKER, JEFFREY M. (Contact) jbecker@utk.edu PROFESSOR NAIDER, FRED R. PROFESSOR

Abstract: DESCRIPTION (provided by applicant): G protein-coupled receptors (GPCRs) comprise the largest family of eukaryotic membrane proteins and are among the most widely-studied biological molecules due to their role as targets for many drugs used in human medicine and their involvement in a multitude of human pathologies. An understanding of GPCR activation, structure, and regulation will facilitate the design and synthesis of drugs to treat many diseases. Despite intense and sustained efforts by many scientists over the last twenty-five years, there remain large gaps in our knowledge of the structure and function of GPCRs. The goals of this proposal are to use the S. cerevisiae pheromone alpha-factor and its GPCR receptor Ste2p to develop approaches that can be used to learn about how activated receptors transmit a signal to intracellular G proteins, to acquire information on receptor structure in the resting and ligand-activated state, and to learn how GPCR signaling is regulated. Specifically, we will conduct experiments to: (i) reveal the conformational changes in extracellular and intracellular domains of Ste2p that are triggered by agonist binding or constitutive mutation and define interactions between receptor and G protein, (ii) elucidate the three-dimensional structure of large fragments of GPCRs alone and as part of a reconstituted receptor, and (iii) study the regulation of signal transduction by identifying proteins that interact with the carboxyl-terminus of Ste2p and examine the conformational changes in the C-terminus induced by these interactions. To accomplish these goals we will use molecular biological, biochemical, and biophysical approaches including substituted cysteine accessibility mutagenesis, unnatural amino acid replacement, native chemical ligation, bioluminescent resonance energy transfer, and multidimensional nuclear magnetic resonance spectroscopy. Success in these studies should provide an understanding of GPCR structure and molecular mechanisms of activation, as well as new experimental tools that can be used by investigators studying this important group of human receptors. PUBLIC HEALTH RELEVANCE Peptide hormones control many essential biological processes in all organisms and tissues. Mutations in genes encoding hormone receptors lead to many pathological conditions in humans, and G protein-coupled receptors (GPCRs) are the target of a majority of pharmacological agents used in medicine today. An understanding of mechanism of action of GPCRs, the structure of these integral membrane proteins, and how signal transduction is regulated will fill fundamental gaps in our knowledge to facilitate the design and synthesis of drugs to treat many diseases.

Public Health Relevance: This Public Health Relevance is not available.

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Institution: UNIVERSITY OF TENNESSEE KNOXVILLE

  1. White Avenue KNOXVILLE, TN 379961529
Fiscal Year: 2008 Department: MICROBIOLOGY Project Start: 01-MAY-1978 Project End: 31-JUL-2012 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: SBCB

Grant Number: 2R56GM022086-31A1 Project Title: Peptide-Cell Interactions in Saccharomyces cerevisiae PI Information: Name Email Title NAIDER, FRED R. naider@mail.csi.cuny.edu PROFESSOR

Abstract: This abstract is not available.

Public Health Relevance: This Public Health Relevance is not available.

Thesaurus Terms:

There are no thesaurus terms on file for this project.

Institution: COLLEGE OF STATEN ISLAND Office of Grants & Research NEW YORK, NY 10314 Fiscal Year: 2007 Department: CHEMISTRY Project Start: 01-MAY-1978 Project End: 31-JUL-2009 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: SBCB

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FORM FIELD Comment Comment emaqil frequently fails! The Fax at the College is 718 982 3910. It is the chemistry department and if you want it to come to me it will need to be identified as To Dr. Fred Naider
 
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