Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Apr;3(4):627-34.
doi: 10.1002/cmdc.200700189.

Molecular Models of the Interface Between Anterior Pharynx-Defective Protein 1 (APH-1) and Presenilin Involving GxxxG Motifs

Affiliations

Molecular Models of the Interface Between Anterior Pharynx-Defective Protein 1 (APH-1) and Presenilin Involving GxxxG Motifs

Krzysztof Jozwiak et al. ChemMedChem. .

Abstract

Gamma-secretase is an integral membrane protease, which is a complex of four membrane proteins. Improper functioning of gamma-secretase was found to be critical in the pathogenesis of Alzheimer's disease. Despite numerous efforts, the structure of the protease as well as its proteolytic mechanism remains poorly understood. In this work we constructed a model of interactions between two proteins forming gamma-secretase: APH-1 and presenilin. This interface is based on a highly conserved GxxxGxxxG motif in the APH-1 protein. It can form a tight contact with a small-residue AxxxAxxxG motif in presenilin. Here, four binding modes based on similar structures involving GxxxG motifs in glycophorin and aquaporin were proposed and verified. The resulting best model employs antiparallel orientations of interacting helices and is in agreement with the currently accepted topology of both proteins. This model can be used for further structural characterization of gamma-secretase and its components.

Similar articles

See all similar articles

Cited by 1 article

Publication types

LinkOut - more resources

Feedback