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DOI | 10.1126/science.aav7897 |
De novo design of tunable, pH-driven conformational changes | |
Boyken, Scott E.1,2; Benhaim, Mark A.3; Busch, Florian4; Jia, Mengxuan4; Bick, Matthew J.1,2; Choi, Heejun5; Klima, Jason C.1,2; Chen, Zibo1,2,6; Walkey, Carl1,2; Mileant, Alexander3,6; Sahasrabuddhe, Aniruddha4; Wei, Kathy Y.1,2,7; Hodge, Edgar A.3; Byron, Sarah2; Quijano-Rubio, Alfredo1,2,8; Sankaran, Banumathi9; King, Neil P.1,2; Lippincott-Schwartz, Jennifer5; Wysocki, Vicki H.4; Lee, Kelly K.3,6; Baker, David1,2,10 | |
2019-05-17 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6441页码:658-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | The ability of naturally occurring proteins to change conformation in response to environmental changes is critical to biological function. Although there have been advances in the de novo design of stable proteins with a single, deep free-energy minimum, the design of conformational switches remains challenging. We present a general strategy to design pH-responsive protein conformational changes by precisely preorganizing histidine residues in buried hydrogen-bond networks. We design homotrimers and heterodimers that are stable above pH 6.5 but undergo cooperative, large-scale conformational changes when the pH is lowered and electrostatic and steric repulsion builds up as the network histidine residues become protonated. The transition pH and cooperativity can be controlled through the number of histidine-containing networks and the strength of the surrounding hydrophobic interactions. Upon disassembly, the designed proteins disrupt lipid membranes both in vitro and after being endocytosed in mammalian cells. Our results demonstrate that environmentally triggered conformational changes can now be programmed by de novo protein design. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000468551000028 |
WOS关键词 | CELL-PENETRATING PEPTIDES ; COILED-COIL PEPTIDE ; NONCOVALENT COMPLEXES ; COMPUTATIONAL DESIGN ; PROTEINS ; STABILITY ; BINDING ; MODEL ; PHENIX ; FUSION |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201448 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Washington, Dept Biochem, Seattle, WA 98195 USA; 2.Univ Washington, Inst Prot Design, Seattle, WA 98195 USA; 3.Univ Washington, Dept Med Chem, Seattle, WA 98195 USA; 4.Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA; 5.Howard Hughes Med Inst, Janelia Res Campus, Ashburn, VA 20147 USA; 6.Univ Washington, Grad Program Biol Phys Struct & Design, Seattle, WA 98195 USA; 7.Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA; 8.Univ Washington, Dept Bioengn, Seattle, WA 98195 USA; 9.Lawrence Berkeley Natl Lab, Mol Biophys & Integrated Bioimaging, Berkeley, CA 94720 USA; 10.Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA |
推荐引用方式 GB/T 7714 | Boyken, Scott E.,Benhaim, Mark A.,Busch, Florian,et al. De novo design of tunable, pH-driven conformational changes[J]. SCIENCE,2019,364(6441):658-+. |
APA | Boyken, Scott E..,Benhaim, Mark A..,Busch, Florian.,Jia, Mengxuan.,Bick, Matthew J..,...&Baker, David.(2019).De novo design of tunable, pH-driven conformational changes.SCIENCE,364(6441),658-+. |
MLA | Boyken, Scott E.,et al."De novo design of tunable, pH-driven conformational changes".SCIENCE 364.6441(2019):658-+. |
条目包含的文件 | 条目无相关文件。 |
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