Institut for Biomedicin

Thomas Vorup-Jensen

Structure and allosteric regulation of the αXβ2 integrin I domain

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DOI

  • Thomas Vorup-Jensen
  • Christian Ostermeier, Novartis Pharma AG
  • ,
  • Motomu Shimaoka, Harvard Medical School
  • ,
  • Ulrich Hommel, Novartis Pharma AG
  • ,
  • Timothy A. Springer, Harvard Medical School
  • Patologisk Institut, THG

The integrin αXβ2 (CD11c/CD18, p150,95) binds ligands through the I domain of the αX subunit. Ligands include the complement factor fragment iC3b, a key component in the innate immune defense, which, together with the expression of αXβ2 on dendritic cells and on other leukocytes, suggests a role in the immune response. We now report the structure of the αX I domain resolved at 1.65 Å by x-ray crystallography. To analyze structural requirements for ligand binding we made a mutation in the αX I domain C-terminal helix, which increased the affinity for iC3b ≈200-fold to 2.4 μM compared with the wild-type domain affinity of ≈400 μM. Gel permeation chromatography supported a conformational change between the wild-type and mutated domains. Conservation of allosteric regulation in the αX I domain points to the functional importance of this phenomenon.

OriginalsprogEngelsk
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Vol/bind100
Nummer4
Sider (fra-til)1873-1878
Antal sider6
ISSN0027-8424
DOI
StatusUdgivet - 18 feb. 2003

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