Structure of a presenilin family intramembrane aspartate protease

Xiaochun Li, Shangyu Dang, Chuangye Yan, Xinqi Gong, Jiawei Wang, Yigong Shi

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Presenilin and signal peptide peptidase (SPP) are intramembrane aspartyl proteases that regulate important biological functions in eukaryotes. Mechanistic understanding of presenilin and SPP has been hampered by lack of relevant structural information. Here we report the crystal structure of a presenilin/SPP homologue (PSH) from the archaeon Methanoculleus marisnigri JR1. The protease, comprising nine transmembrane segments (TMs), adopts a previously unreported protein fold. The amino-terminal domain, consisting of TM1-6, forms a horseshoe-shaped structure, surrounding TM7-9 of the carboxy-terminal domain. The two catalytic aspartate residues are located on the cytoplasmic side of TM6 and TM7, spatially close to each other and approximately 8Å into the lipid membrane surface. Water molecules gain constant access to the catalytic aspartates through a large cavity between the amino-and carboxy-terminal domains. Structural analysis reveals insights into the presenilin/SPP family of intramembrane proteases.

Original languageEnglish (US)
Pages (from-to)56-61
Number of pages6
JournalNature
Volume493
Issue number7430
DOIs
StatePublished - Jan 3 2013

Fingerprint

Presenilins
Aspartic Acid
Peptide Hydrolases
Methanomicrobiaceae
Aspartic Acid Proteases
Archaea
Membrane Lipids
Eukaryota
signal peptide peptidase
Water
Proteins

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Li, X., Dang, S., Yan, C., Gong, X., Wang, J., & Shi, Y. (2013). Structure of a presenilin family intramembrane aspartate protease. Nature, 493(7430), 56-61. https://doi.org/10.1038/nature11801

Structure of a presenilin family intramembrane aspartate protease. / Li, Xiaochun; Dang, Shangyu; Yan, Chuangye; Gong, Xinqi; Wang, Jiawei; Shi, Yigong.

In: Nature, Vol. 493, No. 7430, 03.01.2013, p. 56-61.

Research output: Contribution to journalArticle

Li, X, Dang, S, Yan, C, Gong, X, Wang, J & Shi, Y 2013, 'Structure of a presenilin family intramembrane aspartate protease', Nature, vol. 493, no. 7430, pp. 56-61. https://doi.org/10.1038/nature11801
Li, Xiaochun ; Dang, Shangyu ; Yan, Chuangye ; Gong, Xinqi ; Wang, Jiawei ; Shi, Yigong. / Structure of a presenilin family intramembrane aspartate protease. In: Nature. 2013 ; Vol. 493, No. 7430. pp. 56-61.
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