How the headpiece hinge angle is opened: New insights into the dynamics of integrin activation.

How the headpiece hinge angle is opened: New insights into the dynamics of integrin activation. Research Abstract Details 

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How the headpiece hinge angle is opened: New insights into the dynamics of integrin activation. Abstract Text:

Eileen Puklin-Faucher,Mu Gao,Klaus Schulten,Viola Vogel,

How the integrin head transitions to the high-affinity conformation is debated. Although experiments link activation with the opening of the hinge angle between the betaA and hybrid domains in the ligand-binding headpiece, this hinge is closed in the liganded alpha(v)beta3 integrin crystal structure. We replaced the RGD peptide ligand of this structure with the 10th type III fibronectin module (FnIII10) and discovered through molecular dynamics (MD) equilibrations that when the conformational constraints of the leg domains are lifted, the betaA/hybrid hinge opens spontaneously. Together with additional equilibrations on the same nanosecond timescale in which small structural variations impeded hinge-angle opening, these simulations allowed us to identify the allosteric pathway along which ligand-induced strain propagates via elastic distortions of the alpha1 helix to the betaA/hybrid domain hinge. Finally, we show with steered MD how force accelerates hinge-angle opening along the same allosteric pathway. Together with available experimental data, these predictions provide a novel framework for understanding integrin activation.

How the headpiece hinge angle is opened: New insights into the dynamics of integrin activation. Publishing Authors By Initials

E Puklin-Faucher,M Gao,K Schulten,V Vogel,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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How the headpiece hinge angle is opened: New insights into the dynamics of integrin activation. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Journal of cell biology

VOLUME: 175

Page Numbers: 349-60

Journal Abbreviation: J. Cell Biol.

ISSN: 0021-9525

DAY: 23

MONTH: Oct

YEAR: 2006

How the headpiece hinge angle is opened: New insights into the dynamics of integrin activation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 375356

How the headpiece hinge angle is opened: New insights into the dynamics of integrin activation. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: metabolism

Chemical & Substance for Abstract: How the headpiece hinge angle is opened: New insights into the dynamics of integrin activation. Information

Substance Name: arginyl-glycyl-aspartic acid

Registry Number: 99896-85-2

Grant and Affiliation Information for How the headpiece hinge angle is opened: New insights into the dynamics of integrin activation.

AFFILIATION: Department of Materials, Swiss Federal Institute of Technology in Zurich (ETH Zurich), CH-8093 Zurich, Switzerland.

Country: United States

AGENCY: United States NCRR

GRANT: P41RR05969

ACRONYM: RR

MEDLINETA: J Cell Biol

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