Structural biology of intramembrane proteases: Mechanistic insights from rhomboid and S2P to γ-secretase

Linfeng Sun, Xiaochun Li, Yigong Shi

Research output: Contribution to journalReview article

17 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)97-107
Number of pages11
JournalCurrent Opinion in Structural Biology
Volume37
DOIs
StatePublished - Apr 1 2016

Fingerprint

Amyloid Precursor Protein Secretases
Peptide Hydrolases
Presenilins
Aspartic Acid Proteases
Superficial Back Muscles
Lipid Bilayers
Metalloproteases
Serine Proteases
Catalytic Domain
Hydrolysis
Peptides
Membranes
Water
Enzymes
Proteins

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Structural biology of intramembrane proteases : Mechanistic insights from rhomboid and S2P to γ-secretase. / Sun, Linfeng; Li, Xiaochun; Shi, Yigong.

In: Current Opinion in Structural Biology, Vol. 37, 01.04.2016, p. 97-107.

Research output: Contribution to journalReview article

@article{25c050ac7fb2473ebed9c4e5b80a116b,
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.",
author = "Linfeng Sun and Xiaochun Li and Yigong Shi",
year = "2016",
month = "4",
day = "1",
doi = "10.1016/j.sbi.2015.12.008",
language = "English (US)",
volume = "37",
pages = "97--107",
journal = "Current Opinion in Structural Biology",
issn = "0959-440X",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Structural biology of intramembrane proteases

T2 - Mechanistic insights from rhomboid and S2P to γ-secretase

AU - Sun, Linfeng

AU - Li, Xiaochun

AU - Shi, Yigong

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84955507573&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84955507573&partnerID=8YFLogxK

U2 - 10.1016/j.sbi.2015.12.008

DO - 10.1016/j.sbi.2015.12.008

M3 - Review article

C2 - 26811996

AN - SCOPUS:84955507573

VL - 37

SP - 97

EP - 107

JO - Current Opinion in Structural Biology

JF - Current Opinion in Structural Biology

SN - 0959-440X

ER -