title: Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins.
abstract: The carboxyl terminus of presenilin 1 and 2 (PS1 and PS2) binds to the neuron-specific cell adhesion molecule telencephalin (TLN) in the brain. PS1 deficiency results in the abnormal accumulation of TLN in a yet unidentified intracellular compartment. The first transmembrane domain and carboxyl terminus of PS1 form a binding pocket with the transmembrane domain of TLN. Remarkably, 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 model for PS.
authors.affiliation: Laboratory for Neuronal Cell Biology, Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology, KUL-Gasthuisberg, B-3000 Leuven, Belgium. ad@med.kuleuven.ac.be
authors.forename: W G
authors.initials: WG
authors.lastname: Annaert
authors.forename: C
authors.initials: C
authors.lastname: Esselens
authors.forename: V
authors.initials: V
authors.lastname: Baert
authors.forename: C
authors.initials: C
authors.lastname: Boeve
authors.forename: G
authors.initials: G
authors.lastname: Snellings
authors.forename: P
authors.initials: P
authors.lastname: Cupers
authors.forename: K
authors.initials: K
authors.lastname: Craessaerts
authors.forename: B
authors.initials: B
authors.lastname: De Strooper
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D015870:Gene Expression; D006624:Hippocampus / Q000166:cytology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D053764:Presenilin-1; D053766:Presenilin-2; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques
chemical_list: D016564:Amyloid beta-Protein Precursor; C504585:Icam5 protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D053764:Presenilin-1; D053766:Presenilin-2