Is the binding of β-amyloid protein to antichymotrypsin in Alzheimer plaques mediated by a β-strand insertion?

✍ Scribed by Christine M. Lukacs; David W. Christianson

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 606 KB
• Volume: 25
• Category: Article
• ISSN: 0887-3585
• DOI: 10.1002/(sici)1097-0134(199608)25:4<420::aid-prot2>3.0.co;2-h

✦ Synopsis

A growing body of experimental evidence demonstrates that the serpin antichymotrypsin plays a regulatory role in Alzheimer plaque physiology by interacting with the 42 residue p-amyloid protein, and we have used molecular modeling and energy minimization techniques to study this interaction. Based on the unique plasticity of p-sheet elements in antichymotrypsin (as well as other serpins), we conclude that the interaction of the two proteins is mediated by insertion of the N-terminus of p-amyloid into p-sheet C of antichymotrypsin as a pseudo-strand slC. This p-strand insertion requires the displacement of native antichymotrypsin strand slC, which is known to occur partially or completely at different stages of serpin function. Thus, the association of the two proteins in vivo may be facilitated by a particular functional state of the serpin, e.g., the native or protease-complexed state.