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Mechanism of initiation of lipid binding of apolipoprotein A-I

Award Number: SC3GM089564
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Mechanism of initiation of lipid binding of apolipoprotein A-I - Project Summary Apolipoprotein (apo) A-I is a multifunctional protein with a well-established role in reverse cholesterol transport and is an important player in heart disease. It is the main protein component of high-density lipoprotein (HDL), which circulates through plasma promoting cholesterol efflux. While a high-resolution structure is not known yet, extensive biophysical analysis has suggested that the 28 kDa protein is made of two domains, each of which contain amphipathic α-helices for association with lipid surfaces. The C-terminal (CT) domain contains helical segments that initiate lipid binding, and is also the site responsible for self-association. It is a critical part of the protein needed for maturation of lipid-free apoA-I into HDL. Conflicting data exist about the role of the N-terminal (NT) helices in this process, as well as the precise helical segments of the CT domain. We have recently discovered that CT lysine residues are critical for self-association, and were able to create a monomeric version of the protein. To identify apoA-I helical segments important for initiation of lipid binding and self-association, which are closely connected, we developed a chimeric protein. This chimera will be used to identify which helical segments of apoA-I, both NT and CT α-helices, are required for initiation of lipid binding and self-association. To identify the specific amino acid residues of the CT domain required in self-association, site-directed mutagenesis will be employed. All proteins will be expressed in a bacterial expression system, purified by affinity and size-exclusion chromatography, and characterized for structure and function. The results of this study will lead to a much better understanding in the domain organization of this critical apolipoprotein, their structure function relationship, and may also provide opportunities for high-resolution structural analysis using monomeric apoA-I.


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 = -$4,804 )
2025	2022	CALIFORNIA STATE UNIVERSITY LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	12	1/30/2025	NON-COMPETING CONTINUATION	-$4,804
														Subtotal = -$4,804

Issue Date FY: 2022 ( Subtotal = $110,625 )
2022	2022	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	12	6/2/2022	NON-COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2021 ( Subtotal = $110,625 )
2021	2021	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	11	6/22/2021	NON-COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2020 ( Subtotal = $110,625 )
2020	2020	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	001	10	6/11/2020	NON-COMPETING CONTINUATION	$110,625
2020	2017	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	8	5/6/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $110,625

Issue Date FY: 2019 ( Subtotal = $110,625 )
2019	2019	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	9	6/26/2019	COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2017 ( Subtotal = $110,625 )
2017	2017	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	8	7/1/2017	NON-COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2016 ( Subtotal = $110,625 )
2016	2016	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	7	7/4/2016	NON-COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2015 ( Subtotal = $109,875 )
2015	2015	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	6	7/21/2015	NON-COMPETING CONTINUATION	$109,875
														Subtotal = $109,875

Issue Date FY: 2014 ( Subtotal = $109,125 )
2014	2014	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	001	5	8/12/2014	COMPETING CONTINUATION	$109,125
2014	2013	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	8/11/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $109,125

Issue Date FY: 2013 ( Subtotal = $102,820 )
2013	2013	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	12/14/2012	NON-COMPETING CONTINUATION	$95,894
2013	2013	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	001	4	6/14/2013	NON-COMPETING CONTINUATION	$6,926
														Subtotal = $102,820

Issue Date FY: 2012 ( Subtotal = $106,549 )
2012	2012	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	001	3	2/27/2012	NON-COMPETING CONTINUATION	$10,655
2012	2012	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	12/12/2011	NON-COMPETING CONTINUATION	$95,894
														Subtotal = $106,549

Issue Date FY: 2011 ( Subtotal = $106,549 )
2011	2011	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	001	2	6/30/2011	NON-COMPETING CONTINUATION	$9,686
2011	2011	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	12/27/2010	NON-COMPETING CONTINUATION	$96,863
														Subtotal = $106,549

Issue Date FY: 2010 ( Subtotal = $107,625 )
2010	2010	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	12/14/2009	NEW	$107,625
														Subtotal = $107,625

Grand Total All Awards = $1,301,489

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Mechanism of initiation of lipid binding of apolipoprotein A-I

Award Number: SC3GM089564

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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