Microsomal triglyceride transfer protein large subunit is a
protein that in humans is encoded by the MTTP, also known as MTP,
gene.[5][6]
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.[6]
Apolipoprotein B48 on chylomicra and Apolipoprotein B100 on LDL, IDL, and VLDL are important for MTP binding.[citation needed]
MTP adds triglycerides to nascent chylomicrons in the intestine, and to VLDL in the liver.[7]
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.[8]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
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.
Luz JM, Lennarz WJ (1996). "Protein disulfide isomerase: A multifunctional protein of the endoplasmic reticulum". In Feige U, Yahara I, Morimoto RI, Polla BS (eds.). Stress-Inducible Cellular Responses. Experientia Supplementum. Vol. 77. pp. 97–117.
doi:
10.1007/978-3-0348-9088-5_7.
ISBN978-3-0348-9901-7.
PMID8856971.
Wetterau JR, Lin MC, Jamil H (1997). "Microsomal triaglyceride transfer protein". Biochim. Biophys. Acta. 1345 (2): 136–50.
doi:
10.1016/s0005-2760(96)00168-3.
PMID9106493.
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.
PMID9211060.
Wetterau JR, Aggerbeck LP, Bouma ME, et al. (1992). "Absence of microsomal triaglyceride transfer protein in individuals with abetalipoproteinemia". Science. 258 (5084): 999–1001.
Bibcode:
1992Sci...258..999W.
doi:
10.1126/science.1439810.
PMID1439810.
Sharp D, Ricci B, Kienzle B, et al. (1994). "Human microsomal triaglyceride transfer protein large subunit gene structure". Biochemistry. 33 (31): 9057–61.
doi:
10.1021/bi00197a005.
PMID7545943.
Shoulders CC, Narcisi TM, Read J, et al. (1995). "The abetalipoproteinemia gene is a member of the vitellogenin family and encodes an alpha-helical domain". Nat. Struct. Biol. 1 (5): 285–6.
doi:
10.1038/nsb0594-285.
PMID7664034.
S2CID11860468.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4.
doi:
10.1016/0378-1119(94)90802-8.
PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56.
doi:
10.1016/S0378-1119(97)00411-3.
PMID9373149.
Microsomal triglyceride transfer protein large subunit is a
protein that in humans is encoded by the MTTP, also known as MTP,
gene.[5][6]
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.[6]
Apolipoprotein B48 on chylomicra and Apolipoprotein B100 on LDL, IDL, and VLDL are important for MTP binding.[citation needed]
MTP adds triglycerides to nascent chylomicrons in the intestine, and to VLDL in the liver.[7]
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.[8]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
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.
Luz JM, Lennarz WJ (1996). "Protein disulfide isomerase: A multifunctional protein of the endoplasmic reticulum". In Feige U, Yahara I, Morimoto RI, Polla BS (eds.). Stress-Inducible Cellular Responses. Experientia Supplementum. Vol. 77. pp. 97–117.
doi:
10.1007/978-3-0348-9088-5_7.
ISBN978-3-0348-9901-7.
PMID8856971.
Wetterau JR, Lin MC, Jamil H (1997). "Microsomal triaglyceride transfer protein". Biochim. Biophys. Acta. 1345 (2): 136–50.
doi:
10.1016/s0005-2760(96)00168-3.
PMID9106493.
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.
PMID9211060.
Wetterau JR, Aggerbeck LP, Bouma ME, et al. (1992). "Absence of microsomal triaglyceride transfer protein in individuals with abetalipoproteinemia". Science. 258 (5084): 999–1001.
Bibcode:
1992Sci...258..999W.
doi:
10.1126/science.1439810.
PMID1439810.
Sharp D, Ricci B, Kienzle B, et al. (1994). "Human microsomal triaglyceride transfer protein large subunit gene structure". Biochemistry. 33 (31): 9057–61.
doi:
10.1021/bi00197a005.
PMID7545943.
Shoulders CC, Narcisi TM, Read J, et al. (1995). "The abetalipoproteinemia gene is a member of the vitellogenin family and encodes an alpha-helical domain". Nat. Struct. Biol. 1 (5): 285–6.
doi:
10.1038/nsb0594-285.
PMID7664034.
S2CID11860468.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4.
doi:
10.1016/0378-1119(94)90802-8.
PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56.
doi:
10.1016/S0378-1119(97)00411-3.
PMID9373149.