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Structure paper

TitleStructural mechanism of laminin recognition by integrin.
Journal, issue, pagesNat Commun, Vol. 12, Issue 1, Page 4012, Year 2021
Publish dateJun 29, 2021
AuthorsTakao Arimori / Naoyuki Miyazaki / Emiko Mihara / Mamoru Takizawa / Yukimasa Taniguchi / Carlos Cabañas / Kiyotoshi Sekiguchi / Junichi Takagi /
PubMed AbstractRecognition of laminin by integrin receptors is central to the epithelial cell adhesion to basement membrane, but the structural background of this molecular interaction remained elusive. Here, we ...Recognition of laminin by integrin receptors is central to the epithelial cell adhesion to basement membrane, but the structural background of this molecular interaction remained elusive. Here, we report the structures of the prototypic laminin receptor α6β1 integrin alone and in complex with three-chain laminin-511 fragment determined via crystallography and cryo-electron microscopy, respectively. The laminin-integrin interface is made up of several binding sites located on all five subunits, with the laminin γ1 chain C-terminal portion providing focal interaction using two carboxylate anchor points to bridge metal-ion dependent adhesion site of integrin β1 subunit and Asn189 of integrin α6 subunit. Laminin α5 chain also contributes to the affinity and specificity by making electrostatic interactions with large surface on the β-propeller domain of α6, part of which comprises an alternatively spliced X1 region. The propeller sheet corresponding to this region shows unusually high mobility, suggesting its unique role in ligand capture.
External linksNat Commun / PubMed:34188035 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.55 - 3.9 Å
Structure data

EMDB-30342, PDB-7cec:
Structure of alpha6beta1 integrin in complex with laminin-511
Method: EM (single particle) / Resolution: 3.9 Å

PDB-7cea:
Crystal structure of HUTS-4 Fv-clasp fragment
Method: X-RAY DIFFRACTION / Resolution: 2.55 Å

PDB-7ceb:
Crystal structure of alpha6beta1 integrin headpiece
Method: X-RAY DIFFRACTION / Resolution: 2.89 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-MN:
Unknown entry

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
KeywordsIMMUNE SYSTEM / Antibody fragment / Fv-clasp / Integrin / CELL ADHESION/IMMUNE SYSTEM / Laminin / CELL ADHESION / CELL ADHESION-IMMUNE SYSTEM complex

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