An Evaluation of the Crystal Structure of C-terminal Truncated Apolipoprotein A-I in Solution Reveals Structural Dynamics Related to Lipid Binding

作者：Melchior John T; Walker Ryan G; Morris Jamie; Jones Martin K; Segrest Jere P; Lima Diogo B; Carvalho Paulo C; Gozzo Fabio C; Castleberry Mark; Thompson Thomas B; Davidson W Sean

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 291(10): 5439-5451.

DOI：10.1074/jbc.M115.706093

• apolipoprotein
• mass spectrometry (MS)
• oligomerization
• small-angle x-ray scattering (SAXS)
• structural biology
• structural model

Apolipoprotein (apo) A-I mediates many of the anti-atherogenic functions attributed to high density lipoprotein. Unfortunately, efforts toward a high resolution structure of full-length apoA-I have not been fruitful, although there have been successes with deletion mutants. Recently, a C-terminal truncation (apoA-I185-243) was crystallized as a dimer. The structure showed two helical bundles connected by a long, curved pair of swapped helical domains. To compare this structure to that existing under solution conditions, we applied small angle x-ray scattering and isotope-assisted chemical cross-linking to apoA-I185-243 in its dimeric and monomeric forms. For the dimer, we found evidence for the shared domains and aspects of the N-terminal bundles, but not the molecular curvature seen in the crystal. We also found that the N-terminal bundles equilibrate between open and closed states. Interestingly, this movement is one of the transitions proposed during lipid binding. The monomer was consistent with a model in which the long shared helix doubles back onto the helical bundle. Combined with the crystal structure, these data offer an important starting point to understand the molecular details of high density lipoprotein biogenesis.

• 出版日期2016-3-4