title: Structural biology of presenilins and signal peptide peptidases.
abstract: Presenilin and signal peptide peptidase are multispanning intramembrane-cleaving proteases with a conserved catalytic GxGD motif. Presenilin comprises the catalytic subunit of γ-secretase, a protease responsible for the generation of amyloid-β peptides causative of Alzheimer disease. Signal peptide peptidase proteins are implicated in the regulation of the immune system. Both protease family proteins have been recognized as druggable targets for several human diseases, but their detailed structure still remains unknown. Recently, the x-ray structures of some archaeal GxGD proteases have been determined. We review the recent progress in biochemical and biophysical probing of the structure of these atypical proteases.
authors.affiliation: Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan. taisuke@mol.f.utokyo.ac.jp
authors.forename: Taisuke
authors.initials: T
authors.lastname: Tomita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwatsubo
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001105:Archaea / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D019843:Archaeal Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D020134:Catalytic Domain; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D053763:Presenilins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D019843:Archaeal Proteins; D008565:Membrane Proteins; D053763:Presenilins; D053829:Amyloid Precursor Protein Secretases; D012697:Serine Endopeptidases; C026515:type I signal peptidase
keywords: Intramembrane Proteolysis; Membrane Proteins; Presenilin; Proteolytic Enzymes; Secretases