TY - JOUR
T1 - NMR Solution Structure of the Integral Membrane Enzyme DsbB
T2 - Functional Insights into DsbB-Catalyzed Disulfide Bond Formation
AU - Zhou, Yunpeng
AU - Cierpicki, Tomasz
AU - Jimenez, Ricardo H.Flores
AU - Lukasik, Stephen M.
AU - Ellena, Jeffrey F.
AU - Cafiso, David S.
AU - Kadokura, Hiroshi
AU - Beckwith, Jon
AU - Bushweller, John H.
N1 - Funding Information:
This work was supported by grants R01 GM078296 to J.H.B. and R01 GM41883 to J.B. from the National Institutes of Health.
PY - 2008/9/26
Y1 - 2008/9/26
N2 - We describe the NMR structure of DsbB, a polytopic helical membrane protein. DsbB, a bacterial cytoplasmic membrane protein, plays a key role in disulfide bond formation. It reoxidizes DsbA, the periplasmic protein disulfide oxidant, using the oxidizing power of membrane-embedded quinones. We determined the structure of an interloop disulfide bond form of DsbB, an intermediate in catalysis. Analysis of the structure and interactions with substrates DsbA and quinone reveals functionally relevant changes induced by these substrates. Analysis of the structure, dynamics measurements, and NMR chemical shifts around the interloop disulfide bond suggest how electron movement from DsbA to quinone through DsbB is regulated and facilitated. Our results demonstrate the extraordinary utility of NMR for functional characterization of polytopic integral membrane proteins and provide insights into the mechanism of DsbB catalysis.
AB - We describe the NMR structure of DsbB, a polytopic helical membrane protein. DsbB, a bacterial cytoplasmic membrane protein, plays a key role in disulfide bond formation. It reoxidizes DsbA, the periplasmic protein disulfide oxidant, using the oxidizing power of membrane-embedded quinones. We determined the structure of an interloop disulfide bond form of DsbB, an intermediate in catalysis. Analysis of the structure and interactions with substrates DsbA and quinone reveals functionally relevant changes induced by these substrates. Analysis of the structure, dynamics measurements, and NMR chemical shifts around the interloop disulfide bond suggest how electron movement from DsbA to quinone through DsbB is regulated and facilitated. Our results demonstrate the extraordinary utility of NMR for functional characterization of polytopic integral membrane proteins and provide insights into the mechanism of DsbB catalysis.
KW - PROTEINS
UR - http://www.scopus.com/inward/record.url?scp=52049098074&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=52049098074&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2008.08.028
DO - 10.1016/j.molcel.2008.08.028
M3 - Article
C2 - 18922471
AN - SCOPUS:52049098074
SN - 1097-2765
VL - 31
SP - 896
EP - 908
JO - Molecular Cell
JF - Molecular Cell
IS - 6
ER -