title: Structural biology of intramembrane proteases: mechanistic insights from rhomboid and S2P to γ-secretase.
abstract: Intramembrane proteases catalyze hydrolysis of peptide bond within the lipid bilayer and play a key role in a variety of cellular processes. These membrane-embedded enzymes comprise four major classes: rhomboid serine proteases, site-2 metalloproteases, Rce1-type glutamyl proteases, and aspartyl proteases exemplified by signal peptide peptidase and γ-secretase. In the past several years, three-dimensional structures of representative members of these four classes of intramembrane protease have been reported at atomic resolutions, which reveal distinct protein folds and active site configurations. These structures, together with structure-guided biochemical analyses, shed light on the working mechanisms of water access and substrate entry. In this review, we discuss the shared as well as unique features of these intramembrane proteases, with a focus on presenilin-the catalytic component of γ-secretase.
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: slf09@mails.tsinghua.edu.cn.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Sun
authors.affiliation: Laboratory of Cell Biology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Li
authors.affiliation: Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: shi-lab@tsinghua.edu.cn.
authors.forename: Yigong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D059748:Proteolysis
chemical_list: D008565:Membrane Proteins; D053829:Amyloid Precursor Protein Secretases; D010447:Peptide Hydrolases