LDL receptor

1AJJ, 1D2J, 1F5Y, 1HJ7, 1HZ8, 1I0U, 1IJQ, 1LDL, 1LDR, 1N7D, 1XFE, 2FCW, 2KRI, 2LGP, 2W2M, 2W2N, 2W2O, 2W2P, 2W2Q, 3BPS, 3GCW, 3GCX, 3M0C, 3SO6, 2M7P, 2MG9, 3P5B, 3P5C, 4NE9394916835ENSG00000130164ENSMUSG00000032193P01130P35951NM_001195803NM_001252658NM_001252659NM_010700NP_000518NP_001182727NP_001182728NP_001182729NP_001182732NP_001239587NP_001239588NP_034830The Low-Density Lipoprotein (LDL) Receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognizes the apoprotein B100, which is embedded in the outer phospholipid layer of LDL particles. The receptor also recognizes the apoE protein found in chylomicron remnants and VLDL remnants (IDL). In humans, the LDL receptor protein is encoded by the LDLR gene on chromosome 19. It belongs to the Low density lipoprotein receptor gene family. It is most significantly expressed in bronchial epithelial cells and adrenal gland and cortex tissue.1ajj: LDL RECEPTOR LIGAND-BINDING MODULE 5, CALCIUM-COORDINATING1d2j: LDL RECEPTOR LIGAND-BINDING MODULE 61f5y: NMR STRUCTURE OF A CONCATEMER OF THE FIRST AND SECOND LIGAND-BINDING MODULES OF THE HUMAN LDL RECEPTOR1f8z: NMR STRUCTURE OF THE SIXTH LIGAND-BINDING MODULE OF THE LDL RECEPTOR1hj7: NMR STUDY OF A PAIR OF LDL RECEPTOR CA2+ BINDING EPIDERMAL GROWTH FACTOR-LIKE DOMAINS, 20 STRUCTURES1hz8: SOLUTION STRUCTURE AND BACKBONE DYNAMICS OF A CONCATEMER OF EGF-HOMOLOGY MODULES OF THE HUMAN LOW DENSITY LIPOPROTEIN RECEPTOR1i0u: SOLUTION STRUCTURE AND BACKBONE DYNAMICS OF A CONCATEMER OF EGF-HOMOLOGY MODULES OF THE HUMAN LOW DENSITY LIPOPROTEIN RECEPTOR1ijq: Crystal Structure of the LDL Receptor YWTD-EGF Domain Pair1ldl: THREE-DIMENSIONAL STRUCTURE OF A CYSTEINE-RICH REPEAT FROM THE LOW-DENSITY LIPOPROTEIN RECEPTOR1ldr: SECOND REPEAT OF THE LDL RECEPTOR LIGAND-BINDING DOMAIN1n7d: Extracellular domain of the LDL receptor1xfe: Solution structure of the LA7-EGFA pair from the LDL receptor2fcw: Structure of a Complex Between the Pair of the LDL Receptor Ligand-Binding Modules 3-4 and the Receptor Associated Protein (RAP). The Low-Density Lipoprotein (LDL) Receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognizes the apoprotein B100, which is embedded in the outer phospholipid layer of LDL particles. The receptor also recognizes the apoE protein found in chylomicron remnants and VLDL remnants (IDL). In humans, the LDL receptor protein is encoded by the LDLR gene on chromosome 19. It belongs to the Low density lipoprotein receptor gene family. It is most significantly expressed in bronchial epithelial cells and adrenal gland and cortex tissue. Michael S. Brown and Joseph L. Goldstein were awarded the 1985 Nobel Prize in Physiology or Medicine for their identification of LDL-R and its relation to cholesterol metabolism and familial hypercholesterolemia. The LDLR gene also contains one of 27 SNPs associated with increased risk of coronary artery disease. The LDLR gene resides on chromosome 19 at the band 19p13.2 and is split into 18 exons. Exon 1 contains a signal sequence that localises the receptor to the endoplasmic reticulum for transport to the cell surface. Beyond this, exons 2-6 code the ligand binding region; 7-14 code the epidermal growth factor (EGF) domain; 15 codes the oligosaccharide rich region; 16 (and some of 17) code the membrane spanning region; and 18 (with the rest of 17) code the cytosolic domain. This gene produces 6 isoforms through alternative splicing. This protein belongs to the LDLR family and is made up of a number of functionally distinct domains, including 3 EGF-like domains, 7 LDL-R class A domains, and 6 LDL-R class B repeats. The N-terminal domain of the LDL receptor, which is responsible for ligand binding, is composed of seven sequence repeats (~50% identical). Each repeat, referred to as a class A repeat or LDL-A, contains roughly 40 amino acids, including 6 cysteine residues that form disulfide bonds within the repeat. Additionally, each repeat has highly conserved acidic residues which it uses to coordinate a single calcium ion in an octahedral lattice. Both the disulfide bonds and calcium coordination are necessary for the structural integrity of the domain during the receptor's repeated trips to the highly acidic interior of the endosome. The exact mechanism of interaction between the class A repeats and ligand (LDL) is unknown, but it is thought that the repeats act as 'grabbers' to hold the LDL. Binding of ApoB requires repeats 2-7 while binding ApoE requires only repeat 5 (thought to be the ancestral repeat). Next to the ligand binding domain is an EGF precursor homology domain (EGFP domain). This shows approximately 30% homology with the EGF precursor gene. There are three 'growth factor' repeats; A, B and C. A and B are closely linked while C is separated by the YWTD repeat region, which adopts a beta-propeller conformation (LDL-R class B domain). It is thought that this region is responsible for the pH-dependent conformational shift that causes bound LDL to be released in the endosome. A third domain of the protein is rich in O-linked oligosaccharides but appears to show little function. Knockout experiments have confirmed that no significant loss of activity occurs without this domain. It has been speculated that the domain may have ancestrally acted as a spacer to push the receptor beyond the extracellular matrix. The single transmembrane domain of 22 (mostly) non-polar residues crosses the plasma membrane in a single alpha helix.