image: The structure of C99 in a micelle (depicted as the sphere -- a type of model membrane) is illustrated as a ribbon diagram that traces the protein backbone. This structure was determined using nuclear magnetic resonance (NMR) spectroscopy. The two most striking finds are the presence of a surface-associated "N-helix" just before the transmembrane domain (TMD) and the fact that the TMD is highly curved. The researchers also found that the TMD is not only curved, but flexible.C99 is the 99 residue transmembrane C-terminal domain of the amyloid precursor protein (APP). C99 is the product of beta-secretase cleavage of C99 and itself serves as the substrate for cleavage by gamma-secretase that releases the amyloid-beta peptide, which is believed to form aggregates that trigger Alzheimer’s disease. This image relates to a paper that appeared in the June 1, 2012, issue of Science, published by AAAS. The paper, by P.J. Barrett at Vanderbilt University School of Medicine in Nashville, Tenn., and colleagues was titled, "The Amyloid Precursor Protein Has a Flexible Transmembrane Domain and Binds Cholesterol." view more
Credit: Image courtesy of Charles Sanders, Professor of Biochemistry, Vanderbilt University School of Medicine