TY - JOUR
T1 - Crystal Structure of the 3.8-MDa Respiratory Supermolecule Hemocyanin at 3.0 Å Resolution
AU - Gai, Zuoqi
AU - Matsuno, Asuka
AU - Kato, Koji
AU - Kato, Sanae
AU - Khan, Md Rafiqul Islam
AU - Shimizu, Takeshi
AU - Yoshioka, Takeya
AU - Kato, Yuki
AU - Kishimura, Hideki
AU - Kanno, Gaku
AU - Miyabe, Yoshikatsu
AU - Terada, Tohru
AU - Tanaka, Yoshikazu
AU - Yao, Min
N1 - Funding Information:
We thank Prof. Isao Tanaka of Hokkaido University (Japan) for his helpful discussions. This work was supported by JSPS KAKENHI , grant numbers 26291008 , 24000011 , 26102501 (to Y.T.) and 25450298 (to S.K.), Platform for Drug Discovery, Informatics, and Structural Life Science (to S.K. and Y.T.), and Regional Innovation Strategy Support Program (to S.K., T.S., T.Y., and Y.K.) from the Ministry of Education, Culture, Sports, Science and Technology (Japan). The X-ray diffraction experiments were performed under the proposal numbers 2013G165, 2015G067 (Photon Factory), 2013A6829, 2013A1096, 2013B6829, 2013B1031, 2014A1193, 2014B6930, 2014B1295, 2014B1292, 2015A6524, 2015A1114 (SPring-8), and 20121296 (Swiss Light Source).
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Summary Molluscan hemocyanin, a copper-containing oxygen transporter, is one of the largest known proteins. Although molluscan hemocyanins are currently applied as immunotherapeutic agents, their precise structure has not been determined because of their enormous size. Here, we have determined the first X-ray crystal structure of intact molluscan hemocyanin. The structure unveiled the architecture of the 3.8-MDa supermolecule composed of homologous functional units (FUs), wherein the dimers of FUs hierarchically associated to form the entire cylindrical decamer. Most of the specific inter-FU interactions were localized at narrow regions in the FU dimers, suggesting that rigid FU dimers formed by specific interactions assemble with flexibility. Furthermore, the roles of carbohydrates in assembly and allosteric effect, and conserved sulfur-containing residues in copper incorporation, were revealed. The precise structural information obtained in this study will accelerate our understanding of the molecular basis of hemocyanin and its future applications.
AB - Summary Molluscan hemocyanin, a copper-containing oxygen transporter, is one of the largest known proteins. Although molluscan hemocyanins are currently applied as immunotherapeutic agents, their precise structure has not been determined because of their enormous size. Here, we have determined the first X-ray crystal structure of intact molluscan hemocyanin. The structure unveiled the architecture of the 3.8-MDa supermolecule composed of homologous functional units (FUs), wherein the dimers of FUs hierarchically associated to form the entire cylindrical decamer. Most of the specific inter-FU interactions were localized at narrow regions in the FU dimers, suggesting that rigid FU dimers formed by specific interactions assemble with flexibility. Furthermore, the roles of carbohydrates in assembly and allosteric effect, and conserved sulfur-containing residues in copper incorporation, were revealed. The precise structural information obtained in this study will accelerate our understanding of the molecular basis of hemocyanin and its future applications.
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U2 - 10.1016/j.str.2015.09.008
DO - 10.1016/j.str.2015.09.008
M3 - Article
C2 - 26602184
AN - SCOPUS:84949203424
SN - 0969-2126
VL - 23
SP - 2204
EP - 2212
JO - Structure with Folding & design
JF - Structure with Folding & design
IS - 12
ER -