Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Allosteric Regulation of Actin Capping Protein: Mechanism and Significance

Award Number: R35GM144082
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: 01/19/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

Group Awards By:

View Award Description

Allosteric Regulation of Actin Capping Protein: Mechanism and Significance - Project Summary/Abstract Actin assembly underlies and drives many biological phenomena. Barbed ends of actin filaments, the major sites of polymerization, are controlled by the heterodimeric actin capping protein (CP). CP is regulated by the direct binding of CPI-motif proteins and the protein V-1. These two classes of regulators, CPI-motif proteins and V-1, bind to opposite sides of CP, and they induce conformational changes in CP that allosterically antagonize the binding of the other class. We are studying the molecular biophysical mechanism of these allosteric regulators. We are also studying the physiological function of CP and its regulators, using biochemical reconstitution with purified components, along with molecular genetic perturbations of living cells. Our biochemical studies will test a novel hypothesis for how CP regulators function in cells. Cells contain stoichiometric amounts of V-1 in micromolar concentrations, sufficient to inhibit nearly all of the cellular CP. V-1 is highly diffusible, and V-1 sterically blocks the ability of CP to cap actin filaments. CPI-motif proteins are targeted to membranes, and their CPI motifs allosterically induce the dissociation of V- 1, thus activating CP locally at the membrane. We are testing this hypothesis by determining the molecular biophysical mechanism of the allostery, and by testing the functions of the CPI-motif proteins with respect to cell motility and migration. We have discovered key differences in the biochemical activities of different families of CPI-motif proteins, and we are now using that information to investigate the allosteric mechanism, by combining single-molecule FRET measurements with molecular dynamics simulations. In addition, we are using purified proteins and lipids in a biochemical reconstitution system that induces actin assembly at a surface, thereby mimicking actin polymerization at cellular membranes. We are also using our discoveries about biochemical activities of CPI motifs to test cellular functions of CPI-motif proteins, using chimeras constructed from different CPI- motif proteins with molecular genetic perturbations and real-time movies of the motility phenomena of living cells. Our cell motility assays employ a system of endothelial cell monolayers with transmigrating immune and cancer cells, mimicking the physiological process of transendothelial migration.


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 = $545,421 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Biomedical Research and Research Training	000	5	1/13/2026	NON-COMPETING CONTINUATION	$490,879
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Biomedical Research and Research Training	001	5	3/20/2026	NON-COMPETING CONTINUATION	$54,542
														Subtotal = $545,421

Issue Date FY: 2025 ( Subtotal = $545,421 )
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Biomedical Research and Research Training	002	4	8/12/2025	NON-COMPETING CONTINUATION	$54,542
2025	2025	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Biomedical Research and Research Training	001	4	12/11/2024	NON-COMPETING CONTINUATION	$490,879
2025	2024	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Biomedical Research and Research Training	000	3	11/6/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $545,421

Issue Date FY: 2024 ( Subtotal = $545,421 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Biomedical Research and Research Training	001	3	6/27/2024	NON-COMPETING CONTINUATION	$54,542
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Biomedical Research and Research Training	000	3	12/11/2023	NON-COMPETING CONTINUATION	$490,879
														Subtotal = $545,421

Issue Date FY: 2023 ( Subtotal = $603,529 )
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Biomedical Research and Research Training	002	2	7/25/2023	SUPPLEMENT FOR EXPANSION	$54,600
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Biomedical Research and Research Training	001	2	3/21/2023	NON-COMPETING CONTINUATION	$54,893
2023	2023	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Biomedical Research and Research Training	000	2	12/22/2022	NON-COMPETING CONTINUATION	$494,036
														Subtotal = $603,529

Issue Date FY: 2022 ( Subtotal = $552,436 )
2022	2022	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Biomedical Research and Research Training	000	1	1/19/2022	NEW	$552,436
														Subtotal = $552,436

Grand Total All Awards = $2,792,228

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Allosteric Regulation of Actin Capping Protein: Mechanism and Significance

Award Number: R35GM144082

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: 01/19/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer