Characterization of the monomeric form of the transmembrane and cytoplasmic domains of the integrin β3 subunit by NMR spectroscopy

R Li, CR Babu, K Valentine, JD Lear, AJ Wand… - Biochemistry, 2002 - ACS Publications
R Li, CR Babu, K Valentine, JD Lear, AJ Wand, JS Bennett, WF DeGrado
Biochemistry, 2002ACS Publications
We have characterized a membrane protein containing residues P688− T762 of the integrin
β3 subunit, encompassing its transmembrane and cytoplasmic domains, by nuclear
magnetic resonance spectroscopy. Under conditions in which it is monomeric in
dodecylphosphocholine micelles, the protein consists mainly of α-helical structures. An
amino-terminal helix corresponding to the β3 transmembrane helix extends into the
membrane-proximal region of the cytoplasmic domain. Moreover, following an apparent …
We have characterized a membrane protein containing residues P688−T762 of the integrin β3 subunit, encompassing its transmembrane and cytoplasmic domains, by nuclear magnetic resonance spectroscopy. Under conditions in which it is monomeric in dodecylphosphocholine micelles, the protein consists mainly of α-helical structures. An amino-terminal helix corresponding to the β3 transmembrane helix extends into the membrane-proximal region of the cytoplasmic domain. Moreover, following an apparent hinge at residues H722−D723, residues K725−A735 are mostly α-helical. In the presence of membrane-mimicking detergents, the cytoplasmic domain connected to the transmembrane helix is substantially ordered at pH 4.8 and 50 °C. Its carboxyl-terminal end takes on a turn−helix configuration characteristic of the immunoreceptor tyrosine-based activation motif. These structural features of the β3 subunit should help to explain its interaction with numerous cytosolic interacting proteins and begin to illuminate the mechanism of integrin activation.
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