The structure of a receptor with two associating transmembrane domains on the cell surface: integrin alphaIIbbeta3.
The structure of a receptor with two associating transmembrane domains on the cell surface: integrin alphaIIbbeta3.
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DOI:
10.1016/j.molcel.2009.02.022
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发表时间:
2009-04-24
期刊:
影响因子:
16
通讯作者:
Springer, Timothy A.
中科院分区:
文献类型:
--
作者:
Zhu, Jieqing;Luo, Bing-Hao;Barth, Patrick;Schonbrun, Jack;Baker, David;Springer, Timothy A.
Structures of intact receptors with single-pass transmembrane (TM) domains are essential to understand how extracellular and cytoplasmic domains regulate association and signaling through TM domains. A chemical and computational method to determine structures of the membrane regions of such receptors on the cell surface is developed here and validated with glycophorin. An integrin heterodimer structure reveals association over most of the lengths of the α and β TM domains, and that the principles governing association of hetero and homo TM dimers differ. A turn at the Gly of the juxtamembrane (JM) GFFKR motif caps the α TM helix, and brings the two Phe of GFFKR into the α/β interface. A JM Lys residue in β also has an important role in the interface. The structure is incompatible with previous NMR JM/cytoplasmic complex structures, and together with NMR structures of isolated α and β TM domains, shows how TM association/dissociation regulates integrin signaling. A joint ectodomain and membrane structure shows that substantial flexibility between the extracellular and TM domains is compatible with TM signaling.
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