Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins

The carboxyl terminus of presenilin 1 and 2 (PS1 and PS2) binds to the neur on-specific cell adhesion molecule telencephalin (TLN) in the brain. PS1 de ficiency results in the abnormal accumulation of TLN in a yet unidentified intracellular compartment. The first transmembrane domain and carboxyl term inus of PS1 form a binding pocket with the transmembrane domain of TLN. Rem arkably, APP binds to the same regions via part of its transmembrane domain encompassing the critical residues mutated in familial Alzheimer's disease . Our data surprisingly indicate a spatial dissociation between the binding site and the proposed catalytic site near the critical aspartates in PSs. They provide important experimental evidence to support a ring structure mo del for PS.