气候变化领域集成服务门户(CCPortal): Transferrin receptor targeting by de novo sheet extension

CCPortal

DOI	10.1073/pnas.2021569118
	Transferrin receptor targeting by de novo sheet extension
	Sahtoe D.D.; Coscia A.; Mustafaoglu N.; Miller L.M.; Olal D.; Vulovic I.; Yu T.-Y.; Goreshnik I.; Lin Y.-R.; Clark L.; Busch F.; Stewart L.; Wysocki V.H.; Ingber D.E.; Abraham J.; Baker D.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	The de novo design of polar protein–protein interactions is challenging because of the thermodynamic cost of stripping water away from the polar groups. Here, we describe a general approach for designing proteins which complement exposed polar backbone groups at the edge of beta sheets with geometrically matched beta strands. We used this approach to computationally design small proteins that bind to an exposed beta sheet on the human transferrin receptor (hTfR), which shuttles interacting proteins across the blood–brain barrier (BBB), opening up avenues for drug delivery into the brain. We describe a design which binds hTfR with a 20 nM Kd, is hyperstable, and crosses an in vitro microfluidic organ-on-a-chip model of the human BBB. Our design approach provides a general strategy for creating binders to protein targets with exposed surface beta edge strands. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Blood–brain barrier; Computational protein design; Drug delivery; Neurological disease; Transferrin receptor
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179766
作者单位	Department of Biochemistry, University of Washington, Seattle, WA 98195, United States; Institute for Protein Design, University of Washington, Seattle, WA 98195, United States; HHMI, University of Washington, Seattle, WA 98195, United States; Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, United States; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, United States; Department of Bioengineering, University of Washington, Seattle, WA 98195, United States; Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, United States; Resource for Native Mass Spectrometry Guided Structural Biology, The Ohio State University, Columbus, OH 43210, United States; Department of Surgery and Vascular Biology Program, Harvard Medical School, Boston Children’s Hospital, Boston, MA 02115, United States; Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridg...
推荐引用方式 GB/T 7714	Sahtoe D.D.,Coscia A.,Mustafaoglu N.,et al. Transferrin receptor targeting by de novo sheet extension[J],2021,118(17).
APA	Sahtoe D.D..,Coscia A..,Mustafaoglu N..,Miller L.M..,Olal D..,...&Baker D..(2021).Transferrin receptor targeting by de novo sheet extension.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Sahtoe D.D.,et al."Transferrin receptor targeting by de novo sheet extension".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).