6y76
From Proteopedia
AP01 - a redesigned transferrin receptor apical domain
Structural highlights
Function[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.[1] Publication Abstract from PubMedSupply of iron into human cells is achieved by iron carrier protein transferrin and its receptor that upon complex formation get internalized by endocytosis. Similarly, the iron needs to be delivered into the brain, and necessitates the transport across the blood-brain barrier. While there are still unanswered questions about these mechanisms, extensive efforts have been made to use the system for delivery of therapeutics into biological compartments. The dimeric form of the receptor, where each subunit consists of three domains, further complicates the detailed investigation of molecular determinants responsible for guiding the receptor interactions with other proteins. Especially the apical domain's biological function has been elusive. To further the study of transferrin receptor, we have computationally decoupled the apical domain for soluble expression, and validated the design strategy by structure determination. Besides presenting a methodology for solubilizing domains, the results will allow for study of apical domain's function. Computational backbone design enables soluble engineering of transferrin receptor apical domain.,Sjostrom DJ, Berger SA, Oberdorfer G, Bjelic S Proteins. 2020 Jun 26. doi: 10.1002/prot.25974. PMID:32592192[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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