View source for 6wrx


==Crystal structure of computationally designed protein 2DS25.1 in complex with the human Transferrin receptor ectodomain==
<StructureSection load='6wrx' size='340' side='right'caption='[[6wrx]], [[Resolution|resolution]] 3.07&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6wrx]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WRX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WRX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.07&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6wrx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wrx OCA], [https://pdbe.org/6wrx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wrx RCSB], [https://www.ebi.ac.uk/pdbsum/6wrx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wrx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TFR1_HUMAN TFR1_HUMAN] Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the heditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site.<ref>PMID:3568132</ref> 
<div style="background-color:#fffaf0;">
== 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<ref>PMID:33879614</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wrx" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transferrin receptor|Transferrin receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Abraham J]]
[[Category: Baker D]]
[[Category: Clark L]]
[[Category: Coscia A]]
[[Category: Olal D]]
[[Category: Sahtoe DD]]