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PMID: 16484367 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The molecular architecture of the metalloprotease FtsH.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 9 ·2006-02-28 ·Pages 3066-71

Bieniossek C, Schalch T, Bumann M, Meister M, Meier R, Baumann U

Abstract

The ATP-dependent integral membrane protease FtsH is universally conserved in bacteria. Orthologs exist in chloroplasts and mitochondria, where in humans the loss of a close FtsH-homolog causes a form of spastic paraplegia. FtsH plays a crucial role in quality control by degrading unneeded or damaged membrane proteins, but it also targets soluble signaling factors like sigma(32) and lambda-CII. We report here the crystal structure of a soluble FtsH construct that is functional in caseinolytic and ATPase assays. The molecular architecture of this hexameric molecule consists of two rings where the protease domains possess an all-helical fold and form a flat hexagon that is covered by a toroid built by the AAA domains. The active site of the protease classifies FtsH as an Asp-zincin, contrary to a previous report. The different symmetries of protease and AAA rings suggest a possible translocation mechanism of the target polypeptide chain into the interior of the molecule where the proteolytic sites are located.

MeSH Terms
Adenosine Triphosphatases/genetics,metabolism Aspartic Acid/genetics,metabolism Bacterial Proteins/chemistry,genetics,metabolism Cell Membrane/chemistry,metabolism Crystallography, X-Ray Membrane Proteins/chemistry,genetics,metabolism Metalloproteases/chemistry,genetics,metabolism Models, Molecular Protein Structure, Quaternary Protein Structure, Tertiary Substrate Specificity Thermotoga maritima/enzymology,genetics
Chemicals
Bacterial Proteins Membrane Proteins Aspartic Acid Metalloproteases Adenosine Triphosphatases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bieniossek Christoph
Departement für Chemie und Biochemie, Universität Bern, Switzerland.
Schalch Thomas
Bumann Mario
Meister Markus
Meier Reto
Baumann Ulrich
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0600031103
Published
2006-02-28
Epub
2006-00-16
Pages
3066-71
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1413944
Subset
IM
Databases
PDB
2CE7, 2CEA
External Links
PubMed source DOI: 10.1073/pnas.0600031103 PMC Full Text View journal details
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