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<!doctype html>
<html lang="en">
<head>
<meta charset="utf-8">
<!-- CUSTOMIZE METADATA HERE -->
<title>Presentation</title>
<meta name="description" content="BI281H Discussion">
<meta name="author" content="Michael J. Harms">
<meta name="apple-mobile-web-app-capable" content="yes" />
<meta name="apple-mobile-web-app-status-bar-style" content="black-translucent" />
<meta name="viewport" content="width=device-width, initial-scale=1.0, maximum-scale=1.0, user-scalable=no, minimal-ui">
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</head>
<body>
<!-- CUSTOMIZE SLIDES HERE -->
<div class="reveal">
<!-- Any section element inside of this container is a slide -->
<div class="slides">
<section>
<p>Review session: <em>tonight</em> at 7 pm in Lawrence 115</p>
<p>First midterm: next Wednesday (10/18) 7 pm in MacKenzie 240C</p>
<p>Midterm will cover up through the end of this week (lectures 1-9, homework 1-3, lab 1-3).</p>
<p style="color:red">If you've talked to me about an alternate exam location/time, please talk to me after class</p>
</section>
<section>
<h2>Protein recognition</h2>
<h4>2016-10-11</h4>
<br/>
</section>
<section>
<h4>Conceptual goals</h4>
<ul>
<li class="fragment">Proteins form <em>specific</em> interactions with molecular partners</li>
<li class="fragment">Specificity is achieved by creating interactions that can only be fulfilled by one partner, not others</li>
<li class="fragment">Interactions are "tuned" to affinities useful for the cell.</li>
</ul>
<h4>Skill goals</h4>
<ul>
<li class="fragment">Use structure-based reasoning to predict relative affinities and specificities of different interactions.</li>
<li class="fragment">Use $K_{D}$ to characterize the strength of interactions</li>
</ul>
</section>
<section>
<h4>Many animals exhibit sexual dimorphism</h4>
<div class="row">
<div class="col-xs-4"><img class="img-responsive" src="https://upload.wikimedia.org/wikipedia/commons/7/79/Male_and_female_pheasant.jpg" /></div>
<div class="col-xs-4"><img class="img-responsive" src="https://media.mnn.com/assets/images/2016/02/dimorphism-mandrill.jpg.990x0_q80_crop-smart.jpg" /></div>
<div class="col-xs-4"><img class="img-responsive" src="https://media.mnn.com/assets/images/2016/02/dimorphism-elephantseal.jpg.990x0_q80_crop-smart.jpg" /></div>
</div>
<div class="row">
<div class="col-xs-4"><img class="img-responsive" src="https://media.mnn.com/assets/images/2016/02/dimorphism-anthochariscardamines.jpg.990x0_q80_crop-smart.jpg" /></div>
<div class="col-xs-4"><img class="img-responsive" src="https://media.mnn.com/assets/images/2016/02/dimorphism-lions.jpg.990x0_q80_crop-smart.jpg" /></div>
<div class="col-xs-4"><img class="img-responsive" src="https://media.mnn.com/assets/images/2016/02/dimorphism-mandarinducks.jpg.990x0_q80_crop-smart.jpg" /></div>
</div>
<div class="row">
<div class="col-xs-4"><img class="img-responsive" src="https://media.mnn.com/assets/images/2016/02/dimorphism-orangutan.jpg.990x0_q80_crop-smart.jpg" /></div>
<div class="col-xs-4"><img class="img-responsive" src="https://media.mnn.com/assets/images/2016/02/dimorphism-peacockfowl.jpg.990x0_q80_crop-smart.jpg" /></div>
<div class="col-xs-4"><img class="img-responsive" src="https://cugau85.files.wordpress.com/2013/01/angler-fish-male.jpg" /></div>
</div>
<small>Wikimedia, mnn.com, zmescience</small>
</section>
<section>
<div class="row">
<div class="col-xs-6">
<img src="presentation-data/08/img/testosterone.png" class="img-responsive" height="100%" width="100%"/>
</div>
<div class="col-xs-6">
<div class="row">Testosterone</div>
<div class="row" align="center">
<img src="presentation-data/08/img/mars-symbol.png" class="img-responsive" height="40%" width="40%"/>
</div>
</div>
</div>
<div class="row">
<div class="col-xs-6">
<img src="presentation-data/08/img/estrogen.png" class="img-responsive" height="100%" width="100%"/>
</div>
<div class="col-xs-6">
<div class="row">Estrogen</div>
<div class="row" align="center">
<img src="presentation-data/08/img/venus-symbol.png" class="img-responsive" height="40%" width="40%"/>
</div>
</div>
</div>
</section>
<section>
<div class="row">
<img src="presentation-data/08/img/sr-function.png" class="img-responsive"/>
</div>
<small><a href="https://www.boundless.com/biology/textbooks/boundless-biology-textbook/the-endocrine-system-37/how-hormones-work-211/intracellular-hormone-receptors-795-12031/images/fig-ch37_02_01/">boundless.com</a></small>
</section>
<section>
<h4>Estrogen and testosterone bind to different receptors, turning on different genes</h4>
<ul>
<li>Estrogen binds to the estrogen receptor</li>
<li>Testosterone binds to the androgen receptor</li>
</ul>
</section>
<section data-background="#000000" data-transition="fade">
<p>Receptors have almost identical steroid binding pockets</p>
<video class="video-responsive" data-autoplay mute loop height="50%" width="50%"/>
<source data-src="presentation-data/08/video/estrogen-receptor.mp4" />
<video>
</section>
<section data-background="#000000" data-transition="fade">
<p>How do almost identical receptors distinguish between almost identical steroids?</p>
<video class="video-responsive" data-autoplay mute loop height="50%" width="50%"/>
<source data-src="presentation-data/08/video/estrogen-receptor.mp4" />
<video>
</section>
<section>
<img src="presentation-data/08/img/steroid-specificity_answer.png" class="img-responsive"/>
<div class="fragment">
<p>Binding <em>specificity</em> is discrimination between steroids.</p>
<p>Specificity is determined by:</p>
<ul>
<li>shape of the pocket</li>
<li>polar interactions</li>
</ul>
</div>
</section>
<section>
<p>Biochemists use <em>dissociation constants</em> ($K_{D}$) to measure binding affinity</p>
<p>$ML \rightleftarrows M + L$</p>
<p>$M$ is <em>macromolecule</em> (protein)</p>
<p>$L$ is <em>ligand</em> (small molecule)</p>
<br/>
<div class="fragment">
$K_{D} = \frac{[M][L]}{[ML]}$
</div>
</section>
<section>
<p>We can measure $K_{D}$ by following $\theta$ versus $[L]$</p>
<div>
<div class="col-xs-6 fragment">
<p>$K_{D} = \frac{[M][L]}{[ML]}$</p>
<p>$[ML] \times K_{D} = [M][L]$</p>
<p>$[ML] = \frac{[M][L]}{K_{D}}$</p>
</div>
<div class="col-xs-6 fragment">
<p>$\theta = \frac{[ML]}{[M] + [ML]}$</p>
<p>$\theta = \frac{[M][L]/K_{D}}{[M] + [M][L]/K_{D}}$</p>
<p>$\theta = \frac{[L]/K_{D}}{1 + [L]/K_{D}}$</p>
<p style="color:blue">$\theta = \frac{1}{1 + K_{D}/[L]}$</p>
</div>
</div>
</section>
<section>
<p class="fragment">The $K_{D}$ is the concentration of $L$ at which $\theta = 0.5$.</p>
<img src="presentation-data/08/img/estradiol-vs-testosterone.png" class="img-responsive" height="80%" width="80%"/>
<small>Chen et al. (2004) <em>JBC</em> 279(32):33855-33864</small>
</section>
<section>
<p>Steroids have only a small range of blood concentrations</p>
<div class="row">
<div class="col-xs-4"></div>
<div class="col-xs-4">Female</div>
<div class="col-xs-4">Male</div>
</div>
<div class="row">
<div class="col-xs-4">Estrogen</div>
<div class="col-xs-4">$0.1-2.0\ nM$</div>
<div class="col-xs-4">$0.05-0.2\ nM$</div>
</div>
<div class="row">
<div class="col-xs-4">Testosterone</div>
<div class="col-xs-4">$0.9-3\ nM$</div>
<div class="col-xs-4">$10-50\ nM$</div>
</div>
<small><a href="https://upload.wikimedia.org/wikipedia/commons/c/cb/Blood_values_sorted_by_mass_and_molar_concentration.png">wikipedia.org</a></small>
</section>
<section>
<p>ER responds to physiological concentrations of <em>estrogen</em> but not <em><span style="color:red">testosterone</span></em></p>
<img src="presentation-data/08/img/er-hormone.png" height="55%" width="55%"/>
</section>
<section>
<p>Is one hydrogen bond, in principle, enough to explain the difference in bindng?</p>
<img src="presentation-data/08/img/er-hormone.png" height="55%" width="55%"/>
</section>
<section>
<p>Summary</p>
<ul>
<li>Proteins can bind to specific molecules in the cellular environment</li>
<li>Specificity is acheived by shape complementarity and polar contacs.</li>
<li>The strength of these interactions is quantified by the <em>Dissociation constant</em> ($K_{D}$)</li>
<li>$K_{D}$ is tuned to the concentration of the molecule in the cell</li>
</ul>
</section>
<section>
<p>Review session: <em>tonight</em> at 7 pm in Lawrence 115</p>
<p>First midterm: next Wednesday (10/18) 7 pm in MacKenzie 240C</p>
<p>Midterm will cover up through the end of this week (lectures 1-9, homework 1-3, lab 1-3).</p>
<p style="color:red">If you've talked to me about an alternate exam location/time, please talk to me after class</p>
</section>
</div>
</div>
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