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Determinants of the Hsp90-client interaction

Award Number: R01GM127675
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: 09/16/2019
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Determinants of the Hsp90-client interaction - !Project Abstract The highly conserved abundant molecular chaperone Hsp90 is a global cellular regulator that interacts with client proteins in a dynamic ATP-dependent cycle to ensure client protein folding, transport and/or assembly into multiprotein complexes. Hsp90- dependent proteins have critical roles in many forms of cancer and neurodegenerative disease as well as cystic fibrosis and other diseases. Our long-term goal is to understand how Hsp90 and cochaperones cooperate in the folding of hundreds of proteins with diverse sequences and structures sufficiently to develop small compounds that only affect subsets of Hsp90 clients. In the first Aim, we will use a novel set of Hsp90 mutants to understand how three cochaperones that bind the closed, ATP and client-bound conformation of Hsp90 fine-tune client folding. The technically innovative second Aim will identify and characterize Hsp90 mutants that affect different subsets of client proteins. Together these studies will enable a better mechanistic understanding of the function of cochaperones in regulating client selection, conformation and activity. Identification of clusters of Hsp90 mutants with similar effects will pave a path towards rational design of compounds with selective effects on Hsp90 clients in vivo. !


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: 2026 ( Subtotal = -$32,984 )
2026	2022	REGENTS OF THE UNIVERSITY OF IDAHO	875 PERIMETER DR	MOSCOW	ID	83844	LATAH	USA	Biomedical Research and Research Training	000	4	4/2/2026	NON-COMPETING CONTINUATION	-$32,984
														Subtotal = -$32,984

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	REGENTS OF THE UNIVERSITY OF IDAHO	875 PERIMETER DR	MOSCOW	ID	83844	LATAH	USA	Biomedical Research and Research Training	001	4	6/21/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2022	REGENTS OF THE UNIVERSITY OF IDAHO	875 PERIMETER DR	MOSCOW	ID	83844	LATAH	USA	Biomedical Research and Research Training	000	4	6/21/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $346,049 )
2022	2022	REGENTS OF THE UNIVERSITY OF IDAHO	875 PERIMETER DR MS 3020	MOSCOW	ID	83844	LATAH	USA	Biomedical Research and Research Training	001	4	8/1/2022	SUPPLEMENT FOR EXPANSION	$61,038
2022	2022	REGENTS OF THE UNIVERSITY OF IDAHO	875 PERIMETER DR MS 3020	MOSCOW	ID	83844	LATAH	USA	Biomedical Research and Research Training	000	4	7/29/2022	NON-COMPETING CONTINUATION	$285,011
														Subtotal = $346,049

Issue Date FY: 2021 ( Subtotal = $338,456 )
2021	2021	REGENTS OF THE UNIVERSITY OF IDAHO	875 PERIMETER DRIVE MS 3020	MOSCOW	ID	83844	LATAH	USA	Biomedical Research and Research Training	000	3	7/28/2021	NON-COMPETING CONTINUATION	$282,916
2021	2021	REGENTS OF THE UNIVERSITY OF IDAHO	875 PERIMETER DRIVE MS 3020	MOSCOW	ID	83844	LATAH	USA	Biomedical Research and Research Training	001	3	9/14/2021	SUPPLEMENT FOR EXPANSION	$55,540
														Subtotal = $338,456

Issue Date FY: 2020 ( Subtotal = $282,309 )
2020	2020	REGENTS OF THE UNIVERSITY OF IDAHO	875 PERIMETER DRIVE MS 3020	MOSCOW	ID	83844	LATAH	USA	Biomedical Research and Research Training	001	2	8/18/2020	NON-COMPETING CONTINUATION	$282,309
2020	2019	REGENTS OF THE UNIVERSITY OF IDAHO	875 PERIMETER DRIVE MS 3020	MOSCOW	ID	83844	LATAH	USA	Biomedical Research and Research Training	000	1	12/31/2019	NEW	$0
														Subtotal = $282,309

Issue Date FY: 2019 ( Subtotal = $280,913 )
2019	2019	REGENTS OF THE UNIVERSITY OF IDAHO	875 PERIMETER DRIVE MS 3020	MOSCOW	ID	83844	LATAH	USA	Biomedical Research and Research Training	000	1	9/16/2019	NEW	$280,913
														Subtotal = $280,913

Grand Total All Awards = $1,214,743

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Determinants of the Hsp90-client interaction

Award Number: R01GM127675

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: 09/16/2019

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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