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Examining Glycine Receptor's Intracellular Domain by Crosslinking-Mass Spectrometry

Award Number: R15GM159232
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/11/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Examining Glycine Receptor's Intracellular Domain by Crosslinking-Mass Spectrometry - Project Summary. While high-resolution structural data are available for members of the pentameric ligand-gated ion channel (pLGIC) superfamily in membrane-mimetic environments, the structure of the intracellular domain (ICD) of these receptors in lipid bilayers remains unresolved. Our aims are to conduct crosslinking mass spectrometric studies (CXMS) to complement current methods and characterize the structure of full-length a1 glycine receptors (GlyRs) in reconstituted bilayers different allosteric states, with a particular focus on the ICD. Specific Aim 1 will use CXMS to interrogate the protein structure of the ICD around single sites of attachment of a variable-length photoactivatable protein-protein crosslinkers distributed over the full length of the ICD as a function of GlyR allostery. Specific Aim 2 will use CXMS to examine lipid-protein interactions as a function of allostery using lipid crosslinkers with their respective photoactivatable moieties at different depths of the bilayer, with a particular focus on the close associations of the ICD with the lipid bilayer. Together, the CXMS approaches used in each Aim will provide insight into the structure of this previously unresolved domain and complement high resolution studies conducted in membrane-mimetic environments.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $512,397 )
2025	2025	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVENUE	PITTSBURGH	PA	15282	ALLEGHENY	USA	Biomedical Research and Research Training	000	1	9/11/2025	NEW	$512,397
														Subtotal = $512,397

Grand Total All Awards = $512,397

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Examining Glycine Receptor's Intracellular Domain by Crosslinking-Mass Spectrometry

Award Number: R15GM159232

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/11/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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