Chaperonin-containing TCP-1 complex directly binds to the cytoplasmic domain of the LOX-1 receptor.
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.
Department of Molecular Cardiology, Texas Heart Institute, Houston, TX 77030, USA. Electronic address: dbakthavatsalam@texasheart.org.
Deenadayalan
D
Bakthavatsalam
National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Roh Hun
RH
Soung
National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
David J
DJ
Tweardy
National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Wah
W
Chiu
Department of Molecular Cardiology, Texas Heart Institute, Houston, TX 77030, USA.
Richard A F
RA
Dixon
Department of Molecular Cardiology, Texas Heart Institute, Houston, TX 77030, USA.
Darren G
DG
Woodside
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D056404:Chaperonin Containing TCP-1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008024:Ligands; D008077:Lipoproteins, LDL / Q000378:metabolism; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D021122:Protein Subunits; D034741:RNA, Small Interfering / Q000235:genetics; D051127:Scavenger Receptors, Class E / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D008024:Ligands; D008077:Lipoproteins, LDL; D046912:Multiprotein Complexes; C495137:OLR1 protein, human; D021122:Protein Subunits; D034741:RNA, Small Interfering; D051127:Scavenger Receptors, Class E; C533304:TCP1 protein, human; C099252:oxidized low density lipoprotein; D056404:Chaperonin Containing TCP-1
Atherosclerosis; CCT complex; Lectin-like oxidized low-density lipoprotein receptor; Protein–protein interaction