Structure and regulation of the LDL-receptor and its gene.
- Authors
- Type
- Published Article
- Journal
- British medical bulletin
- Publication Date
- Oct 01, 1990
- Volume
- 46
- Issue
- 4
- Pages
- 891–916
- Identifiers
- PMID: 2100691
- Source
- Medline
- License
- Unknown
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.