2.A.50.4.1 Diacylglycerol O-acyltransferase 1, DGAT1 or AGRP1, of 488 aas and 9 TMSs. The cryoEM structure has been determined (Wang et al. 2020). It synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans. DGAT1 belongs to the membrane-bound O-acyltransferase (MBOAT) superfamily, members of which are found in all kingdoms of life and are involved in the acylation of lipids and proteins. Wang et al. 2020 addressed how human DGAT1 and other mammalian members of the MBOAT family recognize their substrates and catalyse their reactions. They revealed the structure of human DGAT1 in complex with an oleoyl-CoA substrate. Each DGAT1 protomer has nine transmembrane helices, eight of which form a conserved structural fold, the MBOAT fold. It forms a hollow chamber in the membrane that encloses highly conserved catalytic residues. The chamber has separate entrances for each of the two substrates, fatty acyl-CoA and diacylglycerol. DGAT1 exists as either a homodimer or a homotetramer, and the two forms have similar enzymatic activities. The N terminus of DGAT1 interacts with the neighbouring protomer, and these interactions are required for enzymatic activity (Wang et al. 2020). In liver it plays a role in esterifying exogenous
fatty acids to glycerol and is the major acyl-CoA retinol
acyltransferase in the skin, where it acts to maintain retinoid
homeostasis and prevent retinoid toxicity, leading to skin and hair
disorders. It exhibits additional acyltransferase activities, including acyl
CoA:monoacylglycerol acyltransferase (MGAT), wax monoester and wax
diester synthesis (Ma et al. 2017).
|
Accession Number: | O75907 |
Protein Name: | Diacylglycerol O-acyltransferase 1 |
Length: | 488 |
Molecular Weight: | 55278.00 |
Species: | Homo sapiens (Human) [9606] |
Number of TMSs: | 9 |
Location1 / Topology2 / Orientation3: |
Endoplasmic reticulum membrane1 / Multi-pass membrane protein2 |
Substrate |
acyl-CoA |
---|
1: MGDRGSSRRR RTGSRPSSHG GGGPAAAEEE VRDAAAGPDV GAAGDAPAPA PNKDGDAGVG
61: SGHWELRCHR LQDSLFSSDS GFSNYRGILN WCVVMLILSN ARLFLENLIK YGILVDPIQV
121: VSLFLKDPYS WPAPCLVIAA NVFAVAAFQV EKRLAVGALT EQAGLLLHVA NLATILCFPA
181: AVVLLVESIT PVGSLLALMA HTILFLKLFS YRDVNSWCRR ARAKAASAGK KASSAAAPHT
241: VSYPDNLTYR DLYYFLFAPT LCYELNFPRS PRIRKRFLLR RILEMLFFTQ LQVGLIQQWM
301: VPTIQNSMKP FKDMDYSRII ERLLKLAVPN HLIWLIFFYW LFHSCLNAVA ELMQFGDREF
361: YRDWWNSESV TYFWQNWNIP VHKWCIRHFY KPMLRRGSSK WMARTGVFLA SAFFHEYLVS
421: VPLRMFRLWA FTGMMAQIPL AWFVGRFFQG NYGNAAVWLS LIIGQPIAVL MYVHDYYVLN
481: YEAPAAEA