Roles of multimerization and membrane association in the proteolytic functions of FtsH (HflB)

Authors
Citation
Y. Akiyama et K. Ito, Roles of multimerization and membrane association in the proteolytic functions of FtsH (HflB), EMBO J, 19(15), 2000, pp. 3888-3895
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
EMBO JOURNAL
ISSN journal
0261-4189 → ACNP
Volume
19
Issue
15
Year of publication
2000
Pages
3888 - 3895
Database
ISI
SICI code
0261-4189(20000801)19:15<3888:ROMAMA>2.0.ZU;2-Q
Abstract
FtsH (HflB) is an Escherichia coli ATP-dependent protease that degrades som e integral membrane and cytoplasmic proteins. While anchored to the cytopla smic membrane by the two transmembrane (TM) segments near the N-terminus, i t has a large cytoplasmic domain. The N-terminal region also has a role in homo-oligomerization of this protein. To study the significance of the memb rane integration and oligomer formation, we constructed FtsH derivatives in which the N-terminal region had been deleted or replaced with either the l eucine zipper sequence from Saccharomyces cerevisiae GCN4 protein or TM reg ions from other membrane proteins. The cytoplasmic domain, which was monome ric and virtually inactive, was converted, by the attachment of the leucine zipper, to an oligomer with proteolytic function against a soluble, but no t a membrane-bound substrate. In contrast, chimeric TM-FtsH proteins were a ctive against both substrate classes. We suggest that the cytoplasmic domai n has intrinsic but weak self-interaction ability, which becomes effective with the aid of the leucine zipper or membrane tethering, and that membrane association is essential for FtsH to degrade integral membrane proteins.