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British Medical Bulletin 46:891-916 (1990)
© 1990 The British Council

research-article

Structure and regulation of the LDL- receptor and its gene

A K Soutar and B L Knight

MRC Lipoprotein Team, Hammersmith Hospital London, UK

Abstract

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.


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