An Unusual Allosteric Mobility of the C-Terminal Helix of a High-Affinity L Integrin I Domain Variant Bound to ICAM-5

Hongmin Zhang, Jose M Casasnovas, Moonsoo Jin, Jin-huan Liu, Carl G Gahmberg, Timothy A Springer, Jia-huai Wang

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    Sammanfattning

    Integrins are cell surface receptors that transduce signals bidirectionally across the plasma membrane. The key event of integrin signaling is the allosteric regulation between its ligand-binding site and the C-terminal helix (alpha 7) of integrin's inserted (1) domain. A significant axial movement of the alpha 7 helix is associated with the open, active conformation of integrins. We describe the crystal structure of an engineered high-affinity I domain from the integrin alpha(L)beta(2) (LFA-1) alpha subunit in complex with the N-terminal two domains of ICAM-5, an adhesion molecule expressed in telencephalic neurons. The finding that the a7 helix swings out and inserts into a neighboring I domain in an upside-down orientation in the crystals implies an intrinsically unusual mobility of this helix. This remarkable feature allows the alpha 7 helix to trigger integrin's large-scale conformational changes with little energy penalty. It serves as a mechanistic example of how a weakly bound adhesion molecule works in signaling.
    Originalspråkengelska
    TidskriftMolecular Cell
    Volym31
    Utgåva3
    Sidor (från-till)432-437
    Antal sidor6
    ISSN1097-2765
    DOI
    StatusPublicerad - 2008
    MoE-publikationstypA1 Tidskriftsartikel-refererad

    Citera det här

    Zhang, Hongmin ; Casasnovas, Jose M ; Jin, Moonsoo ; Liu, Jin-huan ; Gahmberg, Carl G ; Springer, Timothy A ; Wang, Jia-huai. / An Unusual Allosteric Mobility of the C-Terminal Helix of a High-Affinity L Integrin I Domain Variant Bound to ICAM-5. I: Molecular Cell. 2008 ; Vol. 31, Nr. 3. s. 432-437.
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    title = "An Unusual Allosteric Mobility of the C-Terminal Helix of a High-Affinity L Integrin I Domain Variant Bound to ICAM-5",
    abstract = "Integrins are cell surface receptors that transduce signals bidirectionally across the plasma membrane. The key event of integrin signaling is the allosteric regulation between its ligand-binding site and the C-terminal helix (alpha 7) of integrin's inserted (1) domain. A significant axial movement of the alpha 7 helix is associated with the open, active conformation of integrins. We describe the crystal structure of an engineered high-affinity I domain from the integrin alpha(L)beta(2) (LFA-1) alpha subunit in complex with the N-terminal two domains of ICAM-5, an adhesion molecule expressed in telencephalic neurons. The finding that the a7 helix swings out and inserts into a neighboring I domain in an upside-down orientation in the crystals implies an intrinsically unusual mobility of this helix. This remarkable feature allows the alpha 7 helix to trigger integrin's large-scale conformational changes with little energy penalty. It serves as a mechanistic example of how a weakly bound adhesion molecule works in signaling.",
    author = "Hongmin Zhang and Casasnovas, {Jose M} and Moonsoo Jin and Jin-huan Liu and Gahmberg, {Carl G} and Springer, {Timothy A} and Jia-huai Wang",
    year = "2008",
    doi = "10.1016/j.molcel.2008.06.022",
    language = "English",
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    pages = "432--437",
    journal = "Molecular Cell",
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    An Unusual Allosteric Mobility of the C-Terminal Helix of a High-Affinity L Integrin I Domain Variant Bound to ICAM-5. / Zhang, Hongmin; Casasnovas, Jose M; Jin, Moonsoo; Liu, Jin-huan; Gahmberg, Carl G; Springer, Timothy A; Wang, Jia-huai.

    I: Molecular Cell, Vol. 31, Nr. 3, 2008, s. 432-437.

    Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

    TY - JOUR

    T1 - An Unusual Allosteric Mobility of the C-Terminal Helix of a High-Affinity L Integrin I Domain Variant Bound to ICAM-5

    AU - Zhang, Hongmin

    AU - Casasnovas, Jose M

    AU - Jin, Moonsoo

    AU - Liu, Jin-huan

    AU - Gahmberg, Carl G

    AU - Springer, Timothy A

    AU - Wang, Jia-huai

    PY - 2008

    Y1 - 2008

    N2 - Integrins are cell surface receptors that transduce signals bidirectionally across the plasma membrane. The key event of integrin signaling is the allosteric regulation between its ligand-binding site and the C-terminal helix (alpha 7) of integrin's inserted (1) domain. A significant axial movement of the alpha 7 helix is associated with the open, active conformation of integrins. We describe the crystal structure of an engineered high-affinity I domain from the integrin alpha(L)beta(2) (LFA-1) alpha subunit in complex with the N-terminal two domains of ICAM-5, an adhesion molecule expressed in telencephalic neurons. The finding that the a7 helix swings out and inserts into a neighboring I domain in an upside-down orientation in the crystals implies an intrinsically unusual mobility of this helix. This remarkable feature allows the alpha 7 helix to trigger integrin's large-scale conformational changes with little energy penalty. It serves as a mechanistic example of how a weakly bound adhesion molecule works in signaling.

    AB - Integrins are cell surface receptors that transduce signals bidirectionally across the plasma membrane. The key event of integrin signaling is the allosteric regulation between its ligand-binding site and the C-terminal helix (alpha 7) of integrin's inserted (1) domain. A significant axial movement of the alpha 7 helix is associated with the open, active conformation of integrins. We describe the crystal structure of an engineered high-affinity I domain from the integrin alpha(L)beta(2) (LFA-1) alpha subunit in complex with the N-terminal two domains of ICAM-5, an adhesion molecule expressed in telencephalic neurons. The finding that the a7 helix swings out and inserts into a neighboring I domain in an upside-down orientation in the crystals implies an intrinsically unusual mobility of this helix. This remarkable feature allows the alpha 7 helix to trigger integrin's large-scale conformational changes with little energy penalty. It serves as a mechanistic example of how a weakly bound adhesion molecule works in signaling.

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    DO - 10.1016/j.molcel.2008.06.022

    M3 - Article

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    EP - 437

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    JF - Molecular Cell

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