Related Experiment Video

Updated: Oct 21, 2025

Mitigation of Blood Borne Cell Attachment to Metal Implants through CD47-Derived Peptide Immobilization
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Mitigation of Blood Borne Cell Attachment to Metal Implants through CD47-Derived Peptide Immobilization

Published on: December 3, 2020

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Structure of the human marker of self 5-transmembrane receptor CD47

Gustavo Fenalti1, Nicolas Villanueva2, Mark Griffith3

  • 1Molecular Structure and Design, Bristol Myers Squibb, San Diego, CA, USA. Gustavo.Fenalti@bms.com.

Nature Communications
|September 2, 2021
PubMed

Insights

The CD47 immune checkpoint protein

Area of Science:

  • Immunology
  • Structural Biology
  • Biochemistry

Background:

  • CD47 is a 5-transmembrane receptor and a cell surface marker of self.
  • It binds SIRPα, inhibiting macrophage phagocytosis.
  • Blocking the CD47/SIRPα interaction is a focus of cancer immunotherapy.

Purpose of the Study:

  • To determine the crystal structure of full-length CD47 bound to the B6H12 antibody.
  • To elucidate the structural role of the CD47 extracellular domain (ECD) and its linker region in immune recognition.

Main Methods:

  • X-ray crystallography
  • Hydrogen-deuterium exchange (HDX)
  • Molecular dynamics (MD) simulations

Main Results:

  • The crystal structure of full-length CD47 bound to B6H12 antibody was determined.
  • A six-residue peptide linker (RVVSWF) tethers the CD47 ECD to the transmembrane domain, forming the SWF loop.
  • The SWF loop inserts key residues into the CD47 extracellular loop region (ECLR), stabilizing the ECD.

Conclusions:

  • The CD47 ECLR architecture, including the SWF loop, stabilizes the ECD for cell surface presentation.
  • These findings offer structural insights into CD47 immune recognition and signaling.
  • Understanding CD47 structure can inform the development of novel cancer therapeutics.

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