TY - JOUR
T1 - Defining a pathway of communication from the C-terminal peptide binding domain to the N-terminal ATPase domain in a AAA protein
AU - Cashikar, Anil G.
AU - Schirmer, Eric C.
AU - Hattendorf, Douglas A.
AU - Glover, John R.
AU - Ramakrishnan, Melarkode S.
AU - Ware, Danielle M.
AU - Lindquist, Susan L.
PY - 2002
Y1 - 2002
N2 - AAA proteins remodel other proteins to affect a multitude of biological processes. Their power to remodel substrates must lie in their capacity to couple substrate binding to conformational changes via cycles of nucleotide binding and hydrolysis, but these relationships have not yet been deciphered for any member. We report that when one AAA protein, Hsp104, engages polypeptide at the C-terminal peptide-binding region, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2) drives a conformational change in the middle region. This, in turn, drives ATP hydrolysis in the N-terminal ATPase domain (NBD1). This interdomain communication pathway can be blocked by mutation in the middle region or bypassed by antibodies that bind there, demonstrating the crucial role this region plays in transducing signals from one end of the molecule to the other.
AB - AAA proteins remodel other proteins to affect a multitude of biological processes. Their power to remodel substrates must lie in their capacity to couple substrate binding to conformational changes via cycles of nucleotide binding and hydrolysis, but these relationships have not yet been deciphered for any member. We report that when one AAA protein, Hsp104, engages polypeptide at the C-terminal peptide-binding region, the ATPase cycle of the C-terminal nucleotide-binding domain (NBD2) drives a conformational change in the middle region. This, in turn, drives ATP hydrolysis in the N-terminal ATPase domain (NBD1). This interdomain communication pathway can be blocked by mutation in the middle region or bypassed by antibodies that bind there, demonstrating the crucial role this region plays in transducing signals from one end of the molecule to the other.
UR - http://www.scopus.com/inward/record.url?scp=0036238432&partnerID=8YFLogxK
U2 - 10.1016/S1097-2765(02)00499-9
DO - 10.1016/S1097-2765(02)00499-9
M3 - Article
C2 - 11983167
AN - SCOPUS:0036238432
SN - 1097-2765
VL - 9
SP - 751
EP - 760
JO - Molecular cell
JF - Molecular cell
IS - 4
ER -