ABCA1 p.Leu44Pro
| Predicted by SNAP2: | A: N (72%), C: N (66%), D: D (53%), E: N (66%), F: N (61%), G: N (53%), H: N (66%), I: N (78%), K: N (82%), M: N (87%), N: N (66%), P: D (63%), Q: N (82%), R: N (78%), S: N (87%), T: N (87%), V: N (78%), W: D (75%), Y: N (57%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, F: N, G: N, H: N, I: N, K: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Identification of an apolipoprotein A-I structural... J Biol Chem. 2004 Jun 4;279(23):24044-52. Epub 2004 Mar 29. Natarajan P, Forte TM, Chu B, Phillips MC, Oram JF, Bielicki JK
Identification of an apolipoprotein A-I structural element that mediates cellular cholesterol efflux and stabilizes ATP binding cassette transporter A1.
J Biol Chem. 2004 Jun 4;279(23):24044-52. Epub 2004 Mar 29., [PMID:15051721]
Abstract [show]
Synthetic peptides were used in this study to identify a structural element of apolipoprotein (apo) A-I that stimulates cellular cholesterol efflux and stabilizes the ATP binding cassette transporter A1 (ABCA1). Peptides (22-mers) based on helices 1 (amino acids 44-65) and 10 (amino acids 220-241) of apoA-I had high lipid binding affinity but failed to mediate ABCA1-dependent cholesterol efflux, and they lacked the ability to stabilize ABCA1. The addition of helix 9 (amino acids 209-219) to either helix 1 (creates a 1/9 chimera) or 10 (9/10 peptide) endowed cholesterol efflux capability and ABCA1 stabilization activity similar to full-length apoA-I. Adding helix 9 to helix 1 or 10 had only a small effect on lipid binding affinity compared with the 22-mer peptides, indicating that helix length and/or determinants on the polar surface of the amphipathic alpha-helices is important for cholesterol efflux. Cholesterol efflux was specific for the structure created by the 1/9 and 9/10 helical combinations, as 33-mers composed of helices 1 and 3 (1/3), 2/9, and 4/9 failed to mediate cholesterol efflux in an ABCA1-dependent manner. Transposing helices 9 and 10 (10/9 peptide) did not change the class Y structure, hydrophobicity, or amphiphilicity of the helical combination, but the topography of negatively charged amino acids on the polar surface was altered, and the 10/9 peptide neither mediated ABCA1-dependent cholesterol efflux nor stabilized ABCA1 protein. These results suggest that a specific structural element possessing a linear array of acidic residues spanning two apoA-I amphipathic alpha-helices is required to mediate cholesterol efflux and stabilize ABCA1.
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No. Sentence Comment
215 The 9/1 peptide was engineered with a proline in place of Leu-44, in keeping with the other 33-mers used in this study.
X
ABCA1 p.Leu44Pro 15051721:215:38
status: NEW