Structural mechanisms of allostery and autoinhibition in JNK family kinases.
Structural mechanisms of allostery and autoinhibition in JNK family kinases.
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DOI：
10.1016/j.str.2012.09.021
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发表时间：
2012-12-05
期刊：
影响因子：
--
通讯作者：
LoGrasso PV
中科院分区：
文献类型：
--
作者：
Laughlin JD;Nwachukwu JC;Figuera-Losada M;Cherry L;Nettles KW;LoGrasso PV
c-Jun N-terminal (JNK) family kinases have a common peptide-docking site used by upstream activating kinases, substrates, scaffold proteins, and phosphatases, where the ensemble of bound proteins determines signaling output. Although there are many JNK structures, little is known about mechanisms of allosteric regulation between the catalytic and peptide-binding sites, and the activation loop, whose phosphorylation is required for catalytic activity. Here, we compare three structures of unliganded JNK3 bound to different peptides. These were compared as a class to structures that differ in binding of peptide, small molecule ligand, or conformation of the kinase activation loop. Peptide binding induced an inhibitory interlobe conformer that was reversed by alterations in the activation loop. Structure class analysis revealed the subtle structural mechanisms for allosteric signaling between the peptide-binding site and activation loop. Biochemical data from isothermal calorimetry, fluorescence energy transfer, and enzyme inhibition demonstrated affinity differences among the three peptides that were consistent with structural observations.
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影响因子：
14.8
作者：
Bruning, John B.;Parent, Alexander A.;Gil, German;Zhao, Min;Nowak, Jason;Pace, Margaret C.;Smith, Carolyn L.;Afonine, Pavel V.;Adams, Paul D.;Katzenellenbogen, John A.;Nettles, Kendall W.
通讯作者：
Nettles, Kendall W.
影响因子：
4
作者：
Chambers, Jeremy W.;Cherry, Lisa;Laughlin, John D.;Figuera-Losada, Mariana;LoGrasso, Philip V.
通讯作者：
LoGrasso, Philip V.
影响因子：
16
作者：
Lee, T;Hoofnagle, AN;Ahn, NG
通讯作者：
Ahn, NG
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
9.9
作者：
Kim, Yoosik;Paroush, Ze'ev;Shvartsman, Stanislav Y.
通讯作者：
Shvartsman, Stanislav Y.