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タイトル別表記
Structures Reveal PKG II’s Selective cGMP Binding Mechanism
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
湯浅, 恵造 The University of Tokushima KAKEN研究者をさがす
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
資料タイプ
学術雑誌論文
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.
掲載誌名
Journal of Biological Chemistry
ISSN
00219258
1083351X
cat書誌ID
AA1202441X
出版者
American Society for Biochemistry and Molecular Biology|Elsevier
291
11
開始ページ
5623
終了ページ
5633
発行日
2016-01-14
権利情報
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
生物資源系