Chaperonin-containing TCP-1 complex directly binds to the cytoplasmic domain of the LOX-1 receptor

Deenadayalan Bakthavatsalam; Roh Hun Soung; David J. Tweardy; Wah Chiu; Richard A.F. Dixon; Darren G. Woodside

doi:10.1016/j.febslet.2014.04.049

Chaperonin-containing TCP-1 complex directly binds to the cytoplasmic domain of the LOX-1 receptor

Deenadayalan Bakthavatsalam, Roh Hun Soung, David J. Tweardy, Wah Chiu, Richard A.F. Dixon, Darren G. Woodside

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a scavenger receptor that binds oxidized low-density lipoprotein (OxLDL) and has a role in atherosclerosis development. The N-terminus intracellular region (cytoplasmic domain) of LOX-1 mediates receptor internalization and trafficking, potentially through intracellular protein interactions. Using affinity isolation, we identified 6 of the 8 components of the chaperonin-containing TCP-1 (CCT) complex bound to LOX-1 cytoplasmic domain, which we verified by coimmunoprecipitation and immunostaining in human umbilical vein endothelial cells. We found that the interaction between CCT and LOX-1 is direct and ATP-dependent and that OxLDL suppressed this interaction. Understanding the association between LOX-1 and the CCT complex may facilitate the design of novel therapies for cardiovascular disease.

Original language	English (US)
Pages (from-to)	2133-2140
Number of pages	8
Journal	FEBS Letters
Volume	588
Issue number	13
DOIs	https://doi.org/10.1016/j.febslet.2014.04.049
State	Published - Jun 13 2014
Externally published	Yes

Keywords

Atherosclerosis
CCT complex
Lectin-like oxidized low-density lipoprotein receptor
Protein-protein interaction

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2014.04.049

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title = "Chaperonin-containing TCP-1 complex directly binds to the cytoplasmic domain of the LOX-1 receptor",

abstract = "Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a scavenger receptor that binds oxidized low-density lipoprotein (OxLDL) and has a role in atherosclerosis development. The N-terminus intracellular region (cytoplasmic domain) of LOX-1 mediates receptor internalization and trafficking, potentially through intracellular protein interactions. Using affinity isolation, we identified 6 of the 8 components of the chaperonin-containing TCP-1 (CCT) complex bound to LOX-1 cytoplasmic domain, which we verified by coimmunoprecipitation and immunostaining in human umbilical vein endothelial cells. We found that the interaction between CCT and LOX-1 is direct and ATP-dependent and that OxLDL suppressed this interaction. Understanding the association between LOX-1 and the CCT complex may facilitate the design of novel therapies for cardiovascular disease.",

keywords = "Atherosclerosis, CCT complex, Lectin-like oxidized low-density lipoprotein receptor, Protein-protein interaction",

author = "Deenadayalan Bakthavatsalam and Soung, {Roh Hun} and Tweardy, {David J.} and Wah Chiu and Dixon, {Richard A.F.} and Woodside, {Darren G.}",

note = "Funding Information: This study was supported by the Texas Heart Institute. The authors thank Heather Leibrecht, MS, and Nicole Stancel, PhD, ELS, of the Texas Heart Institute, for their editorial assistance in the preparation of this manuscript. We also thank Dr. Shanmugam Nagaraj, of the University of Pittsburg, and Dr. Peter Vanderslice, of the Texas Heart Institute, for valuable suggestions. D.G.W. is supported by Grants from the National Institutes of Health ( AI095575 ) and the American Heart Association ( 12GRNT11820024 ). D.J.T. received Grant funding from the Cancer Prevention and Research Institute of Texas ( RP110291 ), and the W.C. lab is funded by a Grant from the National Institutes of Health ( PN2EY016525 ). ",

year = "2014",

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doi = "10.1016/j.febslet.2014.04.049",

language = "English (US)",

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T1 - Chaperonin-containing TCP-1 complex directly binds to the cytoplasmic domain of the LOX-1 receptor

AU - Bakthavatsalam, Deenadayalan

AU - Soung, Roh Hun

AU - Tweardy, David J.

AU - Chiu, Wah

AU - Dixon, Richard A.F.

AU - Woodside, Darren G.

N1 - Funding Information: This study was supported by the Texas Heart Institute. The authors thank Heather Leibrecht, MS, and Nicole Stancel, PhD, ELS, of the Texas Heart Institute, for their editorial assistance in the preparation of this manuscript. We also thank Dr. Shanmugam Nagaraj, of the University of Pittsburg, and Dr. Peter Vanderslice, of the Texas Heart Institute, for valuable suggestions. D.G.W. is supported by Grants from the National Institutes of Health ( AI095575 ) and the American Heart Association ( 12GRNT11820024 ). D.J.T. received Grant funding from the Cancer Prevention and Research Institute of Texas ( RP110291 ), and the W.C. lab is funded by a Grant from the National Institutes of Health ( PN2EY016525 ).

PY - 2014/6/13

Y1 - 2014/6/13

N2 - Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a scavenger receptor that binds oxidized low-density lipoprotein (OxLDL) and has a role in atherosclerosis development. The N-terminus intracellular region (cytoplasmic domain) of LOX-1 mediates receptor internalization and trafficking, potentially through intracellular protein interactions. Using affinity isolation, we identified 6 of the 8 components of the chaperonin-containing TCP-1 (CCT) complex bound to LOX-1 cytoplasmic domain, which we verified by coimmunoprecipitation and immunostaining in human umbilical vein endothelial cells. We found that the interaction between CCT and LOX-1 is direct and ATP-dependent and that OxLDL suppressed this interaction. Understanding the association between LOX-1 and the CCT complex may facilitate the design of novel therapies for cardiovascular disease.

AB - Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a scavenger receptor that binds oxidized low-density lipoprotein (OxLDL) and has a role in atherosclerosis development. The N-terminus intracellular region (cytoplasmic domain) of LOX-1 mediates receptor internalization and trafficking, potentially through intracellular protein interactions. Using affinity isolation, we identified 6 of the 8 components of the chaperonin-containing TCP-1 (CCT) complex bound to LOX-1 cytoplasmic domain, which we verified by coimmunoprecipitation and immunostaining in human umbilical vein endothelial cells. We found that the interaction between CCT and LOX-1 is direct and ATP-dependent and that OxLDL suppressed this interaction. Understanding the association between LOX-1 and the CCT complex may facilitate the design of novel therapies for cardiovascular disease.

KW - Atherosclerosis

KW - CCT complex

KW - Lectin-like oxidized low-density lipoprotein receptor

KW - Protein-protein interaction

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Chaperonin-containing TCP-1 complex directly binds to the cytoplasmic domain of the LOX-1 receptor

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Keywords

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