Computational backbone design enables soluble engineering of transferrin receptor apical domain

Dick J Sjöström, Sarah A Berger, Gustav Oberdorfer, Sinisa Bjelic*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Supply 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.

Original languageEnglish
Pages (from-to)1569-1577
Number of pages9
Issue number12
Early online date26 Jun 2020
Publication statusPublished - 1 Dec 2020


  • iron transport
  • protein design
  • Rosetta
  • transferrin
  • transferrin receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology
  • Biochemistry


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