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#LDL receptor

3 public questions tagged with this topic.

Protein Sorting and Trafficking

Which adapter protein interacts with the NPXY motif of LDL receptors?

LDL receptor internalization requires highly specific recognition cytosolic tail by endocytic co-adaptors bridging to clathrin lattice enhancing efficiency. Tail 50 amino acids contains conserved FXNPXY motif positions 802-807 forming tight beta-turn favored aromatic phenylalanine tyrosine. PTB domains autosomal recessive hypercholesterolemia protein ARH LDLRAP1 and Dab2 Disabled-2 liver recognize NPXY tyrosine hydrophobic pocket interacting also basic residues upstream motif. Adaptors contain additional trafficking domains: clathrin box binding heavy chain terminal domain, AP2 beta2 appendage

Ref: He et al., Biochemistry: NPXY motif of LDLR binds ARH and AP2 adaptor.

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Protein Sorting and Trafficking

Which mutation is associated with Familial Hypercholesterolemia (FH)?

Familial hypercholesterolemia prototypical autosomal co-dominant hyperlipidemia illustrating receptor-mediated endocytosis studied Brown Goldstein Nobel 1985 award. Clinical features elevated plasma LDL two to three fold heterozygotes six fold homozygotes tendon xanthomas cholesterol deposition xanthelasma corneal arcus premature atherosclerotic coronary disease often teens homozygotes severe. Molecular lesion mutations LDLR gene locus 19p13.2 encoding 860 aa receptor 18 exons. Over 2000 pathogenic variants classified five classes: class 1 null no synthesis, class 2 transport defective ER rete

Ref: Genetics Home Reference, Familial Hypercholesterolemia: LDLR mutations on 19p13.2 cause FH.

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Protein Sorting and Trafficking

What is the function of the LDL receptor in receptor-mediated endocytosis?

Maintenance systemic cholesterol homeostasis depends precise receptor-mediated recognition apolipoproteins decorating lipoproteins. Low-density lipoprotein particles contain single copy apolipoprotein B-100 enormous 4536 amino acid amphipathic protein wrapping hydrophobic cholesteryl ester core exposing receptor binding domain rich basic arginine lysine around 3000-4000 position. LDL receptor extracellular region comprises seven cysteine-rich ligand-binding repeats LA1-LA7 each coordinating calcium via acidic residues Complementarity to basic ligand. Additional EGF precursor homology domain be

Ref: Brown & Goldstein, Science 1986 and Nobel Lecture: LDL receptor binds apoB-100.

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