4KU7

Structures of PKGI Reveal a cGMP-Selective Activation Mechanism

4KU7 の概要

• エントリーDOI: 10.2210/pdb4ku7/pdb
• 関連するPDBエントリー: 4KU8
• 分子名称: cGMP-dependent protein kinase 1, IODIDE ION, CYCLIC GUANOSINE MONOPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: cyclic nucleotide binding domain, cgmp, signaling protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : Q13976
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20336.72

構造登録者

Huang, G.Y.,Kim, J.J.,Reger, A.S.,Lorenz, R.,Moon, E.W.,Casteel, D.E.,Sankaran, B.,Herberg, F.W.,Kim, C. (登録日: 2013-05-21, 公開日: 2014-01-15, 最終更新日: 2024-02-28)

主引用文献

Huang, G.Y.,Kim, J.J.,Reger, A.S.,Lorenz, R.,Moon, E.W.,Zhao, C.,Casteel, D.E.,Bertinetti, D.,Vanschouwen, B.,Selvaratnam, R.,Pflugrath, J.W.,Sankaran, B.,Melacini, G.,Herberg, F.W.,Kim, C.
Structural Basis for Cyclic-Nucleotide Selectivity and cGMP-Selective Activation of PKG I.
Structure, 22:116-124, 2014

PubMed Abstract: Cyclic guanosine monophosphate (cGMP) and cyclic AMP (cAMP)-dependent protein kinases (PKG and PKA) are closely related homologs, and the cyclic nucleotide specificity of each kinase is crucial for keeping the two signaling pathways segregated, but the molecular mechanism of cyclic nucleotide selectivity is unknown. Here, we report that the PKG Iβ C-terminal cyclic nucleotide binding domain (CNB-B) is highly selective for cGMP binding, and we have solved crystal structures of CNB-B with and without bound cGMP. These structures, combined with a comprehensive mutagenic analysis, allowed us to identify Leu296 and Arg297 as key residues that mediate cGMP selectivity. In addition, by comparing the cGMP bound and unbound structures, we observed large conformational changes in the C-terminal helices in response to cGMP binding, which were stabilized by recruitment of Tyr351 as a "capping residue" for cGMP. The observed rearrangements of the C-terminal helices provide a mechanical insight into release of the catalytic domain and kinase activation.

PubMed: 24239458
DOI: 10.1016/j.str.2013.09.021

実験手法

X-RAY DIFFRACTION (1.65 Å)