Modified low density lipoproteins binding requires a lysine cluster region in the murine macrophage scavenger receptor class A type II.
Atherosclerosis is a consequence of lipid deposition and foam cell formation in the arterial wall. Macrophage scavenger receptor A II is involved in the uptake of modified low density lipoproteins. It contains an extracellular conserved lysine cluster which has been proposed to form a positively charged groove that interacts with acetylated low density lipoproteins (AcLDL). This study evaluated the role of the murine SRA-II and a lysine mutated SRA-II on AcLDL uptake. Fluorescence labeled AcLDL uptake was quantified using a Laser Scan Cytometer. A significant increase in fluorescence uptake was found in the cells transfected with SRA-II versus those with empty vector. Cells expressing the lysine mutated SRA-II also demonstrated a significant decrease in their uptake of AcLDL. This data supports the concept that the conserved lysine cluster in murine SRA-II is the binding region for AcLDL or contributes to the trimeric structure of SRA-II necessary for AcLDL binding.
Experimental Atherosclerosis Section, Translational Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 5N-111, Bethesda, MD 20892-1422, USA. fleyva1@jhmi.edu
Francisco J
FJ
Leyva
Mark A
MA
Pershouse
Andrij
A
Holian
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D017124:Conserved Sequence / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D004705:Endocytosis; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D051117:Scavenger Receptors, Class A / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014162:Transfection
D008077:Lipoproteins, LDL; D050505:Mutant Proteins; D051117:Scavenger Receptors, Class A; D008239:Lysine