ID | 119314 |
タイトル別表記 | Structures Reveal PKG II’s Selective cGMP Binding Mechanism
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著者 |
Campbell, James C.
Baylor College of Medicine
Kim, Jeong Joo
Baylor College of Medicine|University of Kassel
Li, Kevin Y.
Rice University
Huang, Gilbert Y.
Baylor College of Medicine
Reger, Albert S.
Baylor College of Medicine
Matsuda, Shinya
The University of Tokushima
Sankaran, Banumathi
Lowrence Berkeley National Laboratory
Link, Todd M.
The University of Texas M.D.Anderson Cancer Center
Ladbury, John E.
Baylor College of Medicine|The University of Texas M.D.Anderson Cancer Center|University of Leeds
Casteel, Darren E.
University of California, San Diego
Kim, Choel
Baylor College of Medicine
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資料タイプ |
学術雑誌論文
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抄録 | Membrane-bound cGMP-dependent protein kinase (PKG) II is a key regulator of bone growth, renin secretion, and memory formation. Despite its crucial physiological roles, little is known about its cyclic nucleotide selectivity mechanism due to a lack of structural information. Here, we find that the C-terminal cyclic nucleotide binding (CNB-B) domain of PKGII binds cGMP with higher affinity and selectivity when compared with its N-terminal CNB (CNB-A) domain. To understand the structural basis of cGMP selectivity, we solved co-crystal structures of the CNB domains with cyclic nucleotides. Our structures combined with mutagenesis demonstrate that the guanine-specific contacts at Asp -412 and Arg-415 of the αC-helix of CNB-B are crucial for cGMP selectivity and activation of PKG II. Structural comparison with the cGMP selective CNB domains of human PKG I and Plasmodium falciparum PKG (PfPKG) shows different contacts with the guanine moiety, revealing a unique cGMP selectivity mechanism for PKG II.
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掲載誌名 |
Journal of Biological Chemistry
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ISSN | 00219258
1083351X
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cat書誌ID | AA1202441X
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出版者 | American Society for Biochemistry and Molecular Biology|Elsevier
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巻 | 291
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号 | 11
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開始ページ | 5623
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終了ページ | 5633
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発行日 | 2016-01-14
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権利情報 | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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言語 |
eng
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著者版フラグ |
出版社版
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部局 |
生物資源系
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