About LRP1 protein
Low density lipoprotein receptor-related protein 1 (LRP1) is a receptor located in the cell membrane of cells required in phagocytosis of apoptotic cells and endocytosis mediated by receptor. This protein is also known as alpha-2-macroglobulin receptor (A2MR), as it is involved in early embryonic development-and known as cluster of differentiation 91 (CD91), sometimes apolipoprotein E receptor (APOER). It is encoded on chromosome 12 by LRP1 gene in humans and its expression is ubiquitous. LRP1 belongs to the Low Density Lipoprotein Receptor (LDLR) family protein.
LRP1 is involved in many biological processes and signaling pathways. LRP1 protein is especially playing a key role in lipoprotein metabolism (plasma clearance of chylomicron remnants, cellular lipid homeostasis… but some functions may still be resolved to date); cell motility with kinase-dependent intracellular signaling; Amyloid Precursor Protein (APP) metabolism, and neuronal calcium signaling in neurotransmission. Some diseases such as neurodegenerative one may be caused by dysfunctions of LRP1 pathways. Indeed, LRP1 is able to link proteins from extracellular matrix, growth factor, proteases and their inhibitors.
Structure and interactions of LRP1
LRP1 is composed of two chain non-covalently linked. The α- chain, composed of four ligand-binding domain, is extracellular. These binding domains contain cysteine-rich complement-type repeats. Domains II and IV are responsible of the majority of the protein’s binding. The EGF repeats and β propeller domains allow the release of ligands in endosomes (which have lower pH conditions). The β-chain is the transmembrane domain. It contains a cytoplasmic tail composed of hundred residues. These residues compose two NPxY motifs. These motifs are responsible for the protein’s function, especially in endocytosis and signal transduction.The recombinant human LRP1 isoform is fused with a N-terminal His tag.
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