Biology:Microsomal triglyceride transfer protein
 Generic protein structure example |
Microsomal triglyceride transfer protein large subunit is a protein that in humans is encoded by the MTTP, also known as MTP, gene.[1][2]
MTTP encodes the large subunit of the heterodimeric microsomal triglyceride transfer protein (MTP). Protein disulfide isomerase (PDI) completes the heterodimeric MTP, which has been shown to play a central role in lipoprotein assembly. Mutations in MTTP can cause abetalipoproteinemia.[2]
Apolipoprotein B48 on chylomicra and Apolipoprotein B100 on LDL, IDL, and VLDL are important for MTP binding.[citation needed]
Structure
The large subunit of MTP, also known as the alpha subunit, contains an N-terminal half beta barrel, an alpha helix and a C-terminal lipid binding site that lies between two beta pleated sheets. It is a member of the large lipid transfer protein family, like apolipoprotein B (apo B), with which it interacts, but unlike apo B, it is not secreted. The heterodimer is instead retained in the endoplasmic reticulum due to the presence of a C-terminal KDEL motif on the PDI beta subunit.[3]
Interactive pathway map
Pharmacology
Drugs that inhibit MTTP prevent the assembly of apo B-containing lipoproteins thus inhibiting the synthesis of chylomicrons and VLDL and leading to decrease in plasma levels of LDL-C.
- Lomitapide (Juxtapid) was approved by the US FDA for adjunctive treatment of homozygous familial hypercholesterolemia.
- Dirlotapide (Slentrol) and mitratapide (Yarvitan) are veterinary drugs for the management of obesity in dogs.
References
- ↑ "Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein". Hum Mol Genet 2 (12): 2109–16. Mar 1994. doi:10.1093/hmg/2.12.2109. PMID 8111381.
- ↑ 2.0 2.1 "Entrez Gene: MTTP microsomal triglyceride transfer protein". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4547.
- ↑ "The crystal structure of human microsomal triglyceride transfer protein". Proceedings of the Natural Academy of Sciences of the United States of America 116 (35): 17251–17260. 2019. doi:10.1073/pnas.1903029116. PMID 31395737.
Further reading
- "Protein disulfide isomerase: A multifunctional protein of the endoplasmic reticulum". Stress-Inducible Cellular Responses. Experientia Supplementum. 77. 1996. pp. 97–117. doi:10.1007/978-3-0348-9088-5_7. ISBN 978-3-0348-9901-7.
- "Microsomal triaglyceride transfer protein.". Biochim. Biophys. Acta 1345 (2): 136–50. 1997. doi:10.1016/s0005-2760(96)00168-3. PMID 9106493.
- Gordon DA (1997). "Recent advances in elucidating the role of the microsomal triaglyceride transfer protein in apolipoprotein B lipoprotein assembly.". Curr. Opin. Lipidol. 8 (3): 131–7. doi:10.1097/00041433-199706000-00002. PMID 9211060.
- Ye J (2007). "Reliance of Host Cholesterol Metabolic Pathways for the Life Cycle of Hepatitis C Virus". PLOS Pathog. 3 (8): e108. doi:10.1371/journal.ppat.0030108. PMID 17784784.
- "Absence of microsomal triaglyceride transfer protein in individuals with abetalipoproteinemia". Science 258 (5084): 999–1001. 1992. doi:10.1126/science.1439810. PMID 1439810. Bibcode: 1992Sci...258..999W.
- "Human microsomal triaglyceride transfer protein large subunit gene structure". Biochemistry 33 (31): 9057–61. 1994. doi:10.1021/bi00197a005. PMID 7545943.
- "The abetalipoproteinemia gene is a member of the vitellogenin family and encodes an alpha-helical domain". Nat. Struct. Biol. 1 (5): 285–6. 1995. doi:10.1038/nsb0594-285. PMID 7664034.
- "Transcriptional regulation of human and hamster microsomal triaglyceride transfer protein genes. Cell type-specific expression and response to metabolic regulators". J. Biol. Chem. 269 (46): 28737–44. 1994. doi:10.1016/S0021-9258(19)61967-8. PMID 7961826.
- "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- "Cloning and gene defects in microsomal triaglyceride transfer protein associated with abetalipoproteinaemia". Nature 365 (6441): 65–9. 1993. doi:10.1038/365065a0. PMID 8361539. Bibcode: 1993Natur.365...65S.
- "Mutations of the Microsomal Triglyceride-Transfer–Protein Gene in Abetalipoproteinemia". Am. J. Hum. Genet. 57 (6): 1298–310. 1996. PMID 8533758.
- "A novel abetalipoproteinemia genotype. Identification of a missense mutation in the 97-kDa subunit of the microsomal triaglyceride transfer protein that prevents complex formation with protein disulfide isomerase". J. Biol. Chem. 271 (47): 29945–52. 1997. doi:10.1074/jbc.271.47.29945. PMID 8939939.
- "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- "Multiple molecular chaperones interact with apolipoprotein B during its maturation. The network of endoplasmic reticulum-resident chaperones (ERp72, GRP94, calreticulin, and BiP) interacts with apolipoprotein b regardless of its lipidation state". J. Biol. Chem. 273 (33): 21368–73. 1998. doi:10.1074/jbc.273.33.21368. PMID 9694898.
- "A common binding site on the microsomal triaglyceride transfer protein for apolipoprotein B and protein disulfide isomerase". J. Biol. Chem. 274 (5): 3159–64. 1999. doi:10.1074/jbc.274.5.3159. PMID 9915855.
- "Microsomal triaglyceride transfer protein (MTP) gene mutations in Canadian subjects with abetalipoproteinemia". Hum. Mutat. 15 (3): 294–5. 2000. doi:10.1002/(SICI)1098-1004(200003)15:3<294::AID-HUMU14>3.0.CO;2-E. PMID 10679949.
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