Structure and regulation of the LDL-receptor and its gene.
The structural features necessary for the efficient functioning of the LDL receptor are beginning to emerge from investigation of naturally-occurring and artificially-produced mutations in the gene. Six of the seven repeated sequences in the highly-structured NH2-terminal region are needed for optimal binding of LDL and some of the detailed requirements have been elucidated. The membrane-spanning region is required for insertion of the protein into the plasma membrane, and the cytoplasmic region for internalisation and self-association. Many apparently unrelated mutations affect receptor processing in the Golgi and the role of the carbohydrate chains remains obscure. The main means of regulating LDL-receptor activity is through repression of gene transcription by sterols. This requires a specific element in the promoter region and probably involves more than one transcription factor. Independent effects could be achieved by modulating the activity of these factors.
Soutar
A K
AK
MRC Lipoprotein Team, Hammersmith Hospital, London, UK.
Knight
B L
BL
D005796:Genes; D006801:Humans; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
D011973:Receptors, LDL