6wrw

Crystal structure of computationally designed protein 2DS25.5 in complex with the human Transferrin receptor ectodomain

spinqualitylabelsall models 6wrw, resolution 2.84Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6wrw is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.84Å Ligands: BMA, CA, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 K(d), 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. Transferrin receptor targeting by de novo sheet extension.,Sahtoe DD, Coscia A, Mustafaoglu N, Miller LM, Olal D, Vulovic I, Yu TY, Goreshnik I, Lin YR, Clark L, Busch F, Stewart L, Wysocki VH, Ingber DE, Abraham J, Baker D Proc Natl Acad Sci U S A. 2021 Apr 27;118(17):e2021569118. doi: , 10.1073/pnas.2021569118. PMID:33879614 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transferrin receptor

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