 |
PDBsum entry 3ze1
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Cell adhesion/immune system/peptide
|
PDB id
|
|
|
|
3ze1
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
455 a.a.
|
|
|
|
|
|
|
|
|
|
|
464 a.a.
|
|
|
|
|
|
|
|
|
|
|
216 a.a.
|
|
|
|
|
|
|
|
|
|
|
214 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Complete integrin headpiece opening in eight steps.
|
|
|
Authors
|
|
J.Zhu,
J.Zhu,
T.A.Springer.
|
|
|
Ref.
|
|
J Cell Biol, 2013,
201,
1053-1068.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Carefully soaking crystals with Arg-Gly-Asp (RGD) peptides, we captured eight
distinct RGD-bound conformations of the αIIbβ3 integrin headpiece. Starting
from the closed βI domain conformation, we saw six intermediate βI
conformations and finally the fully open βI with the hybrid domain swung out in
the crystal lattice. The β1-α1 backbone that hydrogen bonds to the Asp side
chain of RGD was the first element to move followed by adjacent to metal
ion-dependent adhesion site Ca(2+), α1 helix, α1' helix, β6-α7 loop, α7
helix, and hybrid domain. We define in atomic detail how conformational change
was transmitted over long distances in integrins, 40 Å from the ligand binding
site to the opposite end of the βI domain and 80 Å to the far end of the
hybrid domain. During these movements, RGD slid in its binding groove toward
αIIb, and its Arg side chain became ordered. RGD concentration requirements in
soaking suggested a >200-fold higher affinity after opening. The
thermodynamic cycle shows how higher affinity pays the energetic cost of opening.
|
|
|
|
|
|
|
