Login
Login

microsomal triglyceride transfer protein

{{short description|Large subunit of microsomal triglyceride transfer protein}}

{{cs1 config|name-list-style=vanc}}

{{distinguish|mitochondrial trifunctional protein}}

{{Infobox_gene}}

Microsomal triglyceride transfer protein large subunit is a protein that in humans is encoded by the MTTP, also known as MTP, gene.{{cite journal |vauthors=Shoulders CC, Brett DJ, Bayliss JD, Narcisi TM, Jarmuz A, Grantham TT, Leoni PR, Bhattacharya S, Pease RJ, Cullen PM | title = Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein | journal = Hum Mol Genet | volume = 2 | issue = 12 | pages = 2109–16 |date=Mar 1994 | pmid = 8111381 | doi =10.1093/hmg/2.12.2109 |display-authors=etal}}{{cite web | title = Entrez Gene: MTTP microsomal triglyceride transfer protein| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4547}}

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.

Apolipoprotein B48 on chylomicra and Apolipoprotein B100 on LDL, IDL, and VLDL are important for MTP binding.{{citation needed|date=October 2023}}

MTP adds triglycerides to nascent chylomicrons in the intestine, and to VLDL in the liver.{{Cite book |last=Katzung |first=Bertram G. |title=Basic & Clinical Pharmacology |date= |publisher=McGraw-Hill Education |year=2018 |isbn=978-1-259-64115-2 |editor-last= |editor-first= |edition=14th |series= |location= |publication-date=2018 |pages=638}}

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.{{cite journal|vauthors=Biterova EI, Isupov MN, Keegan RM, Lebedev AA, Sohail AA, Liaquat I, Alanen HI, Ruddock LW|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=116|issue=35|pages=17251–17260|doi=10.1073/pnas.1903029116|doi-access=free|year=2019|title=The crystal structure of human microsomal triglyceride transfer protein|pmid=31395737|pmc=6717300|bibcode=2019PNAS..11617251B }}

Interactive pathway map

{{StatinPathway_WP430|highlight=Microsomal_triglyceride_transfer_protein}}

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.

References

{{reflist}}

Further reading

{{refbegin | 2}}

  • {{cite book |vauthors=Luz JM, Lennarz WJ |title=Stress-Inducible Cellular Responses |chapter=Protein disulfide isomerase: A multifunctional protein of the endoplasmic reticulum |series=Experientia Supplementum|veditors=Feige U, Yahara I, Morimoto RI, Polla BS|volume=77 |pages= 97–117 |year= 1996 |pmid= 8856971 |doi= 10.1007/978-3-0348-9088-5_7|isbn=978-3-0348-9901-7 }}
  • {{cite journal |vauthors=Wetterau JR, Lin MC, Jamil H |title=Microsomal triaglyceride transfer protein. |journal=Biochim. Biophys. Acta |volume=1345 |issue= 2 |pages= 136–50 |year= 1997 |pmid= 9106493 |doi= 10.1016/s0005-2760(96)00168-3 }}
  • {{cite journal | author=Gordon DA |title=Recent advances in elucidating the role of the microsomal triaglyceride transfer protein in apolipoprotein B lipoprotein assembly. |journal=Curr. Opin. Lipidol. |volume=8 |issue= 3 |pages= 131–7 |year= 1997 |pmid= 9211060 |doi=10.1097/00041433-199706000-00002 }}
  • {{cite journal | author=Ye J |title=Reliance of Host Cholesterol Metabolic Pathways for the Life Cycle of Hepatitis C Virus |journal=PLOS Pathog. |volume=3 |issue= 8 |pages= e108 |year= 2007 |pmid= 17784784 |doi= 10.1371/journal.ppat.0030108 | pmc=1959368 |doi-access=free }}
  • {{cite journal |vauthors=Wetterau JR, Aggerbeck LP, Bouma ME, etal |title=Absence of microsomal triaglyceride transfer protein in individuals with abetalipoproteinemia |journal=Science |volume=258 |issue= 5084 |pages= 999–1001 |year= 1992 |pmid= 1439810 |doi=10.1126/science.1439810 |bibcode=1992Sci...258..999W }}
  • {{cite journal |vauthors=Sharp D, Ricci B, Kienzle B, etal |title=Human microsomal triaglyceride transfer protein large subunit gene structure |journal=Biochemistry |volume=33 |issue= 31 |pages= 9057–61 |year= 1994 |pmid= 7545943 |doi=10.1021/bi00197a005 }}
  • {{cite journal |vauthors=Shoulders CC, Narcisi TM, Read J, etal |title=The abetalipoproteinemia gene is a member of the vitellogenin family and encodes an alpha-helical domain |journal=Nat. Struct. Biol. |volume=1 |issue= 5 |pages= 285–6 |year= 1995 |pmid= 7664034 |doi=10.1038/nsb0594-285 |s2cid=11860468 }}
  • {{cite journal |vauthors=Hagan DL, Kienzle B, Jamil H, Hariharan N |title=Transcriptional regulation of human and hamster microsomal triaglyceride transfer protein genes. Cell type-specific expression and response to metabolic regulators |journal=J. Biol. Chem. |volume=269 |issue= 46 |pages= 28737–44 |year= 1994 |doi=10.1016/S0021-9258(19)61967-8 |pmid= 7961826 |doi-access=free }}
  • {{cite journal |vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides |journal=Gene |volume=138 |issue= 1–2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }}
  • {{cite journal |vauthors=Sharp D, Blinderman L, Combs KA, etal |title=Cloning and gene defects in microsomal triaglyceride transfer protein associated with abetalipoproteinaemia |journal=Nature |volume=365 |issue= 6441 |pages= 65–9 |year= 1993 |pmid= 8361539 |doi= 10.1038/365065a0 |bibcode=1993Natur.365...65S |s2cid=4334532 }}
  • {{cite journal |vauthors=Narcisi TM, Shoulders CC, Chester SA, etal |title=Mutations of the Microsomal Triglyceride-Transfer–Protein Gene in Abetalipoproteinemia |journal=Am. J. Hum. Genet. |volume=57 |issue= 6 |pages= 1298–310 |year= 1996 |pmid= 8533758 | pmc=1801399 }}
  • {{cite journal |vauthors=Rehberg EF, Samson-Bouma ME, Kienzle B, etal |title=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 |journal=J. Biol. Chem. |volume=271 |issue= 47 |pages= 29945–52 |year= 1997 |pmid= 8939939 |doi=10.1074/jbc.271.47.29945 |doi-access=free }}
  • {{cite journal |vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library |journal=Gene |volume=200 |issue= 1–2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 }}
  • {{cite journal |vauthors=Linnik KM, Herscovitz H |title=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 |journal=J. Biol. Chem. |volume=273 |issue= 33 |pages= 21368–73 |year= 1998 |pmid= 9694898 |doi=10.1074/jbc.273.33.21368 |doi-access=free }}
  • {{cite journal |vauthors=Bradbury P, Mann CJ, Köchl S, etal |title=A common binding site on the microsomal triaglyceride transfer protein for apolipoprotein B and protein disulfide isomerase |journal=J. Biol. Chem. |volume=274 |issue= 5 |pages= 3159–64 |year= 1999 |pmid= 9915855 |doi=10.1074/jbc.274.5.3159 |doi-access=free }}
  • {{cite journal |vauthors=Wang J, Hegele RA |title=Microsomal triaglyceride transfer protein (MTP) gene mutations in Canadian subjects with abetalipoproteinemia |journal=Hum. Mutat. |volume=15 |issue= 3 |pages= 294–5 |year= 2000 |pmid= 10679949 |doi= 10.1002/(SICI)1098-1004(200003)15:3<294::AID-HUMU14>3.0.CO;2-E |doi-access= free }}

{{refend}}

{{Lipoprotein metabolism}}

Category:Human proteins

{{gene-4-stub}}