Asymmetric interactions of ATP with the AAA+ ClpX6 unfoldase: allosteric control of a protein machine.
Cell
; 121(7): 1017-27, 2005 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-15989952
ABSTRACT
ATP hydrolysis by AAA+ ClpX hexamers powers protein unfolding and translocation during ClpXP degradation. Although ClpX is a homohexamer, positive and negative allosteric interactions partition six potential nucleotide binding sites into three classes with asymmetric properties. Some sites release ATP rapidly, others release ATP slowly, and at least two sites remain nucleotide free. Recognition of the degradation tag of protein substrates requires ATP binding to one set of sites and ATP or ADP binding to a second set of sites, suggesting a mechanism that allows repeated unfolding attempts without substrate release over multiple ATPase cycles. Our results rule out concerted hydrolysis models involving ClpX(6)*ATP(6) or ClpX(6)*ADP(6) and highlight structures of hexameric AAA+ machines with three or four nucleotides as likely functional states. These studies further emphasize commonalities between distant AAA+ family members, including protein and DNA translocases, helicases, motor proteins, clamp loaders, and other ATP-dependent enzymes.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bacterial Proteins
/
Adenosine Triphosphate
/
Bacterial Proton-Translocating ATPases
/
Escherichia coli Proteins
/
Endopeptidase Clp
Language:
En
Journal:
Cell
Year:
2005
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA