Pulse labeling reveals the tail end of protein folding by proteome profiling.
Pulse labeling reveals the tail end of protein folding by proteome profiling.
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脉冲标记揭示了通过蛋白质组分析的蛋白质折叠的尾端。
DOI：
10.1016/j.celrep.2022.111096
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发表时间：
2022-07-19
期刊：
影响因子：
8.8
通讯作者：
Mayor, Thibault
中科院分区：
文献类型：
--
作者：
Zhu, Mang;Kuechler, Erich R.;Wong, Ryan W. K.;Calabrese, Gaetano;Sitarik, Ian M.;Rana, Viraj;Stoynov, Nikolay;O'Brien, Edward P.;Gsponer, Jorg;Mayor, Thibault
新生蛋白质序列准确和有效地折叠成它们的天然状态需要蛋白质稳态网络的支持。在这里，我们探测哪些新翻译的蛋白质是热敏性的，使它们在热应激下容易发生错误折叠和聚集，使用脉冲SILAC质谱。我们发现一组独特的蛋白质，是高度敏感的这种扰动时，新合成的，但不是一旦成熟。这些蛋白质是丰富的和高度结构化的。值得注意的是，它们显示出形成β折叠二级结构的趋势，具有更复杂的折叠拓扑结构，并且富含分子伴侣结合基序，这表明对分子伴侣辅助折叠的需求更高。与其他蛋白质相比，这些多肽也更经常地是稳定蛋白质复合物的组分。结合这些发现表明，细胞中存在一个特定的蛋白质子集，在达到天然状态之前合成后特别容易发生错误折叠和聚集。Zhu等人揭示了一个蛋白质子集在新合成时更具温度敏感性，但一旦成熟就不会。与其他蛋白质相比，这些蛋白质具有与更复杂的折叠拓扑结构相关的特征，这表明它们在达到其天然状态之前在合成后仍然容易发生错误折叠和聚集。
Accurate and efficient folding of nascent protein sequences into their native states requires support from the protein homeostasis network. Herein we probe which newly translated proteins are thermo-sensitive, making them susceptible to misfolding and aggregation under heat stress using pulse-SILAC mass spectrometry. We find a distinct group of proteins that is highly sensitive to this perturbation when newly synthesized but not once matured. These proteins are abundant and highly structured. Notably, they display a tendency to form β sheet secondary structures, have more complex folding topology, and are enriched for chaperone-binding motifs, suggesting a higher demand for chaperone-assisted folding. These polypeptides are also more often components of stable protein complexes in comparison with other proteins. Combining these findings suggests the existence of a specific subset of proteins in the cell that is particularly vulnerable to misfolding and aggregation following synthesis before reaching the native state. Zhu et al. reveal that a subset of proteins is more thermo-sensitive when newly synthesized but not once matured. These proteins have features associated with more complex folding topology in comparison with other proteins, suggesting they remain susceptible to misfolding and aggregation following synthesis before reaching their native states.
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影响因子：
9.5
作者：
Dabrowski-Tumanski P;Rubach P;Niemyska W;Gren BA;Sulkowska JI
通讯作者：
Sulkowska JI
影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
14.9
作者：
Deutsch EW;Csordas A;Sun Z;Jarnuczak A;Perez-Riverol Y;Ternent T;Campbell DS;Bernal-Llinares M;Okuda S;Kawano S;Moritz RL;Carver JJ;Wang M;Ishihama Y;Bandeira N;Hermjakob H;Vizcaíno JA
通讯作者：
Vizcaíno JA
影响因子：
8.8
作者：
Christiano R;Nagaraj N;Fröhlich F;Walther TC
通讯作者：
Walther TC
影响因子：
4.6
作者：
Baiesi, Marco;Orlandini, Enzo;Trovato, Antonio
通讯作者：
Trovato, Antonio