Peptides derived from transcription factor EB bind to calcineurin at a similar region as the NFAT-type motif.
Peptides derived from transcription factor EB bind to calcineurin at a similar region as the NFAT-type motif.
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从转录因子EB衍生的肽与NFAT型基序相似的区域与钙调蛋白结合。
DOI：
10.1016/j.biochi.2017.09.002
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发表时间：
2017-11
期刊：
影响因子：
3.9
通讯作者：
Luo J
中科院分区：
文献类型：
--
作者：
Song R;Li J;Zhang J;Wang L;Tong L;Wang P;Yang H;Wei Q;Cai H;Luo J
钙调神经磷酸酶（CN）参与许多生理过程，并与多种底物相互作用。大多数底物含有CN识别的相似基序。最近的研究揭示了一种新的CN底物，转录因子EB（TFEB），它参与自噬。我们表明，来自TFEB的15-mer QSYLENPTSYHLQQS肽（TFEB-YLENP）结合CN。将TFEB-YLENP肽转化为YLAVP后，其对CN的亲和力增加，具有更强的CN抑制活性。分子动力学模拟显示TFEB-YLENP肽在CN中具有与活化T细胞的核因子胞质1（NFATc 1-YLAVP）的15-mer DQYLAVPQHPYQWAK基序相同的对接位点。此外，NFATc 1-YLAVP肽的表达抑制了饥饿Hela细胞中TFEB的活化。我们的研究首先在TFEB中鉴定了CN结合位点，并比较了来自CN底物的各种肽的抑制能力。这些数据揭示了细胞内CN信号传导的识别序列的多样性。CN-底物相互作用的研究为开发靶向CN-底物相互作用的选择性CN肽抑制剂奠定了基础。
Calcineurin (CN) is involved in many physiological processes and interacts with multiple substrates. Most of the substrates contain similar motifs recognized by CN. Recent studies revealed a new CN substrate, transcription factor EB (TFEB), which is involved in autophagy. We showed that a 15-mer QSYLENPTSYHLQQS peptide from TFEB (TFEB-YLENP) bound to CN. When the TFEB-YLENP peptide was changed to YLAVP, its affinity for CN increased and it had stronger CN inhibitory activity. Molecular dynamics simulations revealed that the TFEB-YLENP peptide has the same docking sites in CN as the 15-mer DQYLAVPQHPYQWAK motif of the nuclear factor of activated T cells, cytoplasmic 1 (NFATc1-YLAVP). Moreover expression of the NFATc1-YLAVP peptide suppressed the TFEB activation in starved Hela cells. Our studies first identified a CN binding site in TFEB and compared the inhibitory capability of various peptides derived from CN substrates. The data uncovered a diversity in recognition sequences that underlies the CN signaling within the cell. Studies of CN-substrate interactions should lay the groundwork for developing selective CN peptide inhibitors that target CN-substrate interaction in vitro experiments.
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影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
21.3
作者：
Medina DL;Di Paola S;Peluso I;Armani A;De Stefani D;Venditti R;Montefusco S;Scotto-Rosato A;Prezioso C;Forrester A;Settembre C;Wang W;Gao Q;Xu H;Sandri M;Rizzuto R;De Matteis MA;Ballabio A
通讯作者：
Ballabio A
影响因子：
4.4
作者：
Liu, J;Arai, K;Arai, N
通讯作者：
Arai, N
影响因子：
5.7
作者：
Gal, Maayan;Li, Shuai;Wagner, Gerhard
通讯作者：
Wagner, Gerhard
影响因子：
2.9
作者：
Carme Mulero, M.;Orzaez, Mar;Perez-Riba, Merce
通讯作者：
Perez-Riba, Merce