Apolipoprotein structure and dynamics.
OBJECTIVE
This review highlights recent advances in structural studies of exchangeable human apolipoproteins and the insights they provide into lipoprotein action in cardiovascular and amyloid diseases.


RESULTS
The high-resolution X-ray crystal structure of free apoA-II reveals a parallel helical array that may represent other lipid-poor apolipoproteins, and the structure in complex with detergent substantiates the belt model for the protein arrangement on lipoproteins. Nuclear magnetic resonance structures of apolipoprotein-detergent complexes show a repertoire of curved helical conformations, suggesting multiple helical arrangements on the lipid. Low-resolution spectroscopic analyses, interface studies and molecular modeling provide new insights into the 'hinge-domain' mechanism of apolipoprotein adaptation at variable lipoprotein surfaces. A kinetic mechanism for lipoprotein stabilization is proposed.


CONCLUSIONS
Cumulative evidence supports the belt model that provides a general structural basis for understanding the molecular mechanisms of functional apolipoprotein reactions, such as binding to lipoprotein receptors, lipid transporters, and the activation of lipophilic enzymes. However, the detailed protein and lipid conformations on lipoproteins and the underlying molecular interactions are unclear. New insights will hopefully emerge once the first detailed lipoprotein structure is solved.
Gursky
Olga
O
Department of Physiology and Biophysics, Boston University School of Medicine, W329, Boston, Massachusetts 02118, USA. gursky@bu.edu
D001053:Apolipoproteins / Q000737:chemistry* / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D018360:Crystallography, X-Ray; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D019906:Nuclear Magnetic Resonance, Biomolecular
D001053:Apolipoproteins