ABCA1 p.Pro165Ala
| Predicted by SNAP2: | A: D (53%), C: D (71%), D: D (85%), E: D (66%), F: D (80%), G: D (59%), H: D (80%), I: D (75%), K: D (85%), L: D (80%), M: D (71%), N: D (75%), Q: D (71%), R: D (85%), S: N (82%), T: N (72%), V: D (59%), W: D (85%), Y: D (85%), |
| Predicted by PROVEAN: | A: N, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, Q: D, R: D, S: N, T: N, V: D, W: D, Y: D, |
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Probing the pathways of chylomicron and HDL metabo... Curr Opin Lipidol. 2004 Apr;15(2):151-66. Zannis VI, Chroni A, Kypreos KE, Kan HY, Cesar TB, Zanni EE, Kardassis D
Probing the pathways of chylomicron and HDL metabolism using adenovirus-mediated gene transfer.
Curr Opin Lipidol. 2004 Apr;15(2):151-66., [PMID:15017358]
Abstract [show]
PURPOSE OF THE REVIEW: This review clarifies the functions of key proteins of the chylomicron and the HDL pathways. RECENT FINDINGS: Adenovirus-mediated gene transfer of several apolipoprotein (apo)E forms in mice showed that the amino-terminal 1-185 domain of apoE can direct receptor-mediated lipoprotein clearance in vivo. Clearance is mediated mainly by the LDL receptor. The carboxyl-terminal 261-299 domain of apoE induces hypertriglyceridemia, because of increased VLDL secretion, diminished lipolysis and inefficient VLDL clearance. Truncated apoE forms, including apoE2-202, have a dominant effect in remnant clearance and may have future therapeutic applications for the correction of remnant removal disorders. Permanent expression of apoE and apoA-I following adenoviral gene transfer protected mice from atherosclerosis. Functional assays, protein cross-linking, and adenovirus-mediated gene transfer of apoA-I mutants in apoA-I deficient mice showed that residues 220-231, as well as the central helices of apoA-I, participate in ATP-binding cassette transporter A1-mediated lipid efflux and HDL biogenesis. Following apoA-I gene transfer, an amino-terminal deletion mutant formed spherical alpha-HDL, a double amino- and carboxyl-terminal deletion mutant formed discoidal HDL, and a carboxyl-terminal deletion mutant formed only pre-beta-HDL. The findings support a model of cholesterol efflux that requires direct physical interactions between apoA-I and ATP-binding cassette transporter A1, and can explain Tangier disease and other HDL deficiencies. SUMMARY: New insights are provided into the role of apoE in cholesterol and triglyceride homeostasis, and of apoA-I in the biogenesis of HDL. Clearance of the lipoprotein remnants and increase in HDL synthesis are obvious targets for therapeutic interventions.
Comments [show]
None has been submitted yet.
No. Sentence Comment
191 This analysis showed that mutations M1 (apoA-I [Pro165Ala/Gln172Glu]) and M2 (apoA-I[Glu234,235Ala/ Lys238,239Ala]), which do not affect the binding of apoA-I to HDL and the solubilization of multilamellar DMPC vesicles in vitro, are associated with high apoA-I and HDL levels in vivo.
X
ABCA1 p.Pro165Ala 15017358:191:48
status: NEW