1GW4

THE HELIX-HINGE-HELIX STRUCTURAL MOTIF IN HUMAN APOLIPOPROTEIN A-I DETERMINED BY NMR SPECTROSCOPY, 1 STRUCTURE

Summary for 1GW4

• Entry DOI: 10.2210/pdb1gw4/pdb
• Descriptor: APOA-I (1 entity in total)
• Functional Keywords: high density lipoproteins, key in vivo cofactor for the enzyme lecithin-cholesterol transferase, cholesterol efflux, receptor binding, amphipathic helices, helix-hinge-helix motif
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 5151.78

Authors

Wang, G.,Sparrow, J.T.,Cushley, R.J. (deposition date: 1997-06-04, release date: 1997-07-23, Last modification date: 2024-05-22)

Primary citation

Wang, G.,Sparrow, J.T.,Cushley, R.J.
The helix-hinge-helix structural motif in human apolipoprotein A-I determined by NMR spectroscopy.
Biochemistry, 36:13657-13666, 1997

PubMed Abstract: The conformation of a synthetic peptide of 46 residues from apoA-I was investigated by fluorescence, CD, and 2D NMR spectroscopies in lipid-mimetic environments. ApoA-I(142-187) is mainly unstructured in water but helical in SDS or dodecylphosphocholine (DPC), although the peptide only associates with DPC at approximately the critical micellar concentration. Solution structures of apoA-I(142-187) were determined by distance geometry calculations based on 450 (in DPC-d38) or 397 (in SDS-d25) NOE-derived distance restraints, respectively. Backbone RMSDs for superimposing the two helical regions 146-162 and 168-182 are 0.98 +/- 0.22 (2.38 +/- 0.20) and 1.99 +/- 0.42 (2.02 +/- 0.21) A in DPC (SDS), respectively. No interhelical NOE was found, suggesting that helix-helix interactions between the two helical domains in apoA-I(142-187) are unlikely. Similar average, curved helix-hinge-helix structures were found in both SDS and DPC micelles with the hydrophobic residues occupying the concave face, indicating that hydrophobic interactions dominate. Intermolecular NOESY experiments, performed in the presence of 50% protonated SDS, confirm that the two amphipathic helices and Y166 in the hinge all interact with the micelle. The involvement of Y166 in lipid binding is supported by fluorescence spectroscopy as well. On the basis of all the data above, we propose a model for the peptide-lipid complexes wherein the curved amphipathic helix-hinge-helix structural motif straddles the micelle. The peptide-aided signal assignment achieved for apoA-I(122-187) (66mer) and apoA-I suggests that such a structural motif is retained in the longer peptide and most likely in the intact protein.

PubMed: 9354635
DOI: 10.1021/bi971151q

Experimental method

SOLUTION NMR