A Model for Integrin Inside-Out Activation and Clustering

<p>Cellular stimulation induces a conformational change in talin that exposes its talin head domain. The talin head domain binds to the β cytoplasmic tail, which displaces the α tail from its complex with the β tail, which in turn leads to an unclasping and a membrane-associated structural change of the cytoplasmic face (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020169#pbio-0020169-Vinogradova1" target="_blank">Vinogradova et al. 2002</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020169#pbio-0020169-Vinogradova2" target="_blank">2004</a>). Notice the proposed shifted membrane interface for both membrane-proximal helices before and after unclasping (green bars), which suggests a “fanning-out” unclasping process (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020169#pbio-0020169-Vinogradova2" target="_blank">Vinogradova et al. 2004</a>). The unclasping initiates the opening of the integrin C-terminal stalks—including the transmembrane domains (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020169#pbio-0020169-Luo1" target="_blank">Luo et al. 2004</a>)—which is necessary for the switchblade shift of the extracellular headpiece from the bent to the extended form for high-affinity ligand binding (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020169#pbio-0020169-Takagi2" target="_blank">Takagi et al. 2002</a>). The α subunit is in blue and the β subunit is in red. The ligated integrins cluster, possibly via oligomerization of transmembrane domains (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020169#pbio-0020169-Li1" target="_blank">Li et al. 2003</a>). The model was generated based on the crystal structure of α_vβ₃ extracellular domain (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020169#pbio-0020169-Xiong1" target="_blank">Xiong et al. 2001</a>) and the nuclear magnetic resonance structure of the cytoplasmic domain (<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020169#pbio-0020169-Vinogradova1" target="_blank">Vinogradova et al. 2002</a>, <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020169#pbio-0020169-Vinogradova2" target="_blank">2004</a>) with the helices extending to the transmembrane domain.</p

Physicochemical properties of PHA terpolymers: molecular weight characteristics (A), DSC (B), and X-Ray (C).

<p>Physicochemical properties of PHA terpolymers: molecular weight characteristics (A), DSC (B), and X-Ray (C).</p

Surface properties of films from solutions of PHAs with different chemical compositions.

<p>Surface properties of films from solutions of PHAs with different chemical compositions.</p

<i>C. eutrophus</i> B-10646 culture parameters under standard conditions of PHA synthesis (A); at varied initial polymer concentrations in the inoculum (B); and at varied cell concentrations in the inoculum (C).

<p><i>C. eutrophus</i> B-10646 culture parameters under standard conditions of PHA synthesis (A); at varied initial polymer concentrations in the inoculum (B); and at varied cell concentrations in the inoculum (C).</p

Morphology of mouse fibroblast NIH 3T3 cells cultured on films prepared from PHAs with different composition at Day 7 of the culture: FITC and DAPI staining.

<p>Bar  =  100 µ<b>m.</b></p

Chemical composition and properties of PHAs synthesized by <i>Cupriavidus eutrophus</i> B-10646 from glucose supplemented with precursor substrates: propionate+γ-butyrolactone (Samples 1–5) or valerate+hexanoate (Samples 6–8).

<p>Chemical composition and properties of PHAs synthesized by <i>Cupriavidus eutrophus</i> B-10646 from glucose supplemented with precursor substrates: propionate+γ-butyrolactone (Samples 1–5) or valerate+hexanoate (Samples 6–8).</p

Results of MTT assay of mouse fibroblast NIH 3T3 cells cultured on films prepared from PHAs with different composition.

<p>Results of MTT assay of mouse fibroblast NIH 3T3 cells cultured on films prepared from PHAs with different composition.</p

Physical-mechanical properties of films from solutions of PHAs with different chemical composition.

<p>Physical-mechanical properties of films from solutions of PHAs with different chemical composition.</p

AFM of surface topography of polymer films prepared from PHAs with different chemical composition.

<p>AFM of surface topography of polymer films prepared from PHAs with different chemical composition.</p

Parameters of the <i>C. eutrophus</i> B-10646 culture and dynamics of monomer fractions in the PHA in experiments with mixed carbon substrate: glucose+propionate+γ-butyrolactone (A) and glucose+valerate+hexanoate (B).

<p>(↓) The arrow shows additions of precursor substrates to the culture medium (6–8 h after the beginning of cultivation).</p