NMR analysis of structure and dynamics of the cytosolic tails of integrin alpha IIb beta 3 in aqueous solution

Biochemistry. 2001 Jun 26;40(25):7498-508. doi: 10.1021/bi010338l.


The structural and dynamic properties of the cytosolic tails of the adhesion receptor integrin alphaIIbbeta3, fused to a coiled-coil construct via (Gly)(3) linkers, were studied in aqueous solution by nuclear magnetic resonance (NMR) spectroscopy. Both tails were largely flexible and unstructured, although, in the beta3 tail, residues Arg(724)-Ala(735) have a propensity to form a helical structure and residues Asn(744)-Tyr(747) (NPLY) have a propensity to adopt reverse-turn conformations. The mutation beta3(Y747A) disrupted this reverse-turn tendency and markedly reduced the affinity of the head domain of the cytoskeletal protein, talin for the beta3 tail. Omission of the (Gly)(3) linker connecting the coiled-coiled helices and the integrin tails lead to helix propagation into the beta3 tail extending up to eight residues. A variety of different tail constructs were made and studied to reveal tail-tail interactions, but surprisingly no significant interactions between both tails could be detected within the context of our constructs. These results provide structural insight into a highly conserved beta tail motif (NPXY/F) required for integrin signaling and highlight a second transiently structured region (residues Arg(724)-Ala(735)), which might also be of functional significance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Cytosol / chemistry*
  • Integrins / chemistry*
  • Integrins / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Nuclear Magnetic Resonance, Biomolecular / methods
  • Peptide Fragments / chemistry*
  • Peptide Fragments / genetics
  • Platelet Glycoprotein GPIIb-IIIa Complex / chemistry*
  • Platelet Glycoprotein GPIIb-IIIa Complex / genetics
  • Protein Structure, Secondary / genetics
  • Recombinant Fusion Proteins / chemistry
  • Solutions
  • Structure-Activity Relationship
  • Thermodynamics
  • Water


  • Integrins
  • Peptide Fragments
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Recombinant Fusion Proteins
  • Solutions
  • Water