Alice Clark/BRCT

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== '''ATP Synthase''' ==
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<Structure load='6w25' size='350' frame='true' align='right' caption='Melanocrtin 4 Receptor complex with peptide (PDB code [[6w25]])' scene='86/868791/Alices_rainbow_selection/1' />
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<StructureSection load='5lqz' size='350' side='right' caption='ATP Synthase (PDB entry [[5lqz]])' scene='78/781973/Start/1'>
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ATP synthase is shown here to the right ==>
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[[Image:Screenshot_2021-02-25_at_15.36.50.png|350px|right|thumb| MCR1]]
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It is depicted in 3D with each protein shown in a different colour.
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==Melanocortin 1 Receptor: An insight to MCR1 structure, function and regulation==
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===Introduction to MC1R===
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The highly polymorphic human MC1R gene, located on chromosome 16q24.3 encodes for a MCR1 receptor also known as melanocyte -stimulating hormone receptor. The '''melanocortin receptor''' family consists of five members: MC1R, MCR2, MCR3, MC4R and MC5R all of which exhibit functions and are expressed differently (Wolf Horrell, Boulanger and D’Orazio, 2016). The gene is expressed in melanocytes along with other cell types that inhabit the skin such as keratinocytes and fibroblast as well as cells that operate the immune system (Gruis and Doorn, 2012). The activation of the MC1R receptor by ultraviolet radiation increases the production of the dark eumelanin pigment, resulting in the darkening of the skin. MCR1 stimulation also results in increased melanocyte dendricity, proliferation, cell survival and DNA repair. The loss of melanocortin receptor function results in the production of the red/yellow pheomelanin pigment by melanocytes, resulting in the red hair, fair skin, poor tanning, freckling and increased skin cancer risk in humans (Beaumont et al., 2011).
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===Determination of MC1R Structure===
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The mature MC1R protein is made up of 317 amino acids and a 7 a-helical transmembrane domain. Based on the sequence similarity analysis, the melanocortin receptor family belong to the class A of G-coupled protein receptors therefore direct information on their secondary and tertiary structures is limited as G coupled protein receptors are resistant to crystallisation (Garcia-Borron, Sanchez-Laorden and Jimenez-Cervantes, 2005) (Zhao and Wu, 2012).
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<scene name='86/868791/Hennas_protein/1'>hot pink protein</scene>
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MC4R
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Ligands
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<scene name='86/868791/Rainbow_veiw/1'>test rainbow</scene>
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Tools for exploring ATP synthase in 3D
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===3D structures of MC4R===
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- left mouse button to rotate the protein model.
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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- middle mouse button or scroll wheel to zoom (option-click on a Mac)
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[[6w25]] – hMC4R + peptide – human<br />
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[[7aue]], [[7f55]], [[7f58]] – hMC4R in Gs protein complex + nanobody – Cryo EM<br />
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[[7piu]] – hMC4R in Gs protein complex + nanobody + drug – Cryo EM<br />
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[[7f53]], [[7piu]], [[7piv]] – hMC4R in Gs protein complex + nanobody + a-melanocyte-stimulating hormone – Cryo EM<br />
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[[Category:Topic Page]]
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- right mouse button for more options and information (control-click on a Mac).
 
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- green text - click to load a new 3D scene
 
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'''Have a go yourself now ==>'''
 
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'''Exploring the ATP synthase molecule'''
 
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ATP synthase is a cellular molecular motor found in the mitochondrial membrane of humans, and also in other organisms. It has a role in the generation of ATP, the cells energy currency. This large molecule is built up of a number of different groups of proteins: the F0, the F1, and the stator - each group has an important role to play.
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<scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>
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<scene name='pdbligand=4J2:(2R)-2-AMINO-3-(NAPHTHALEN-2-YL)PROPANOIC+ACID'>4J2</scene>
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<scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</scene>, <scene name='pdbligand=YCM:S-(2-AMINO-2-OXOETHYL)-L-CYSTEINE'>YCM</scene>
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The F1 and Axle
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The <scene name='86/868791/Alices_1t15/2'>BRCA Protein</scene> contains an α (alpha) chain (shown in light blue) and a β (beta) chain (shown in dark blue). The <scene name='78/781973/Axel/1'>axle</scene>, rotates (like the axle on a car), and is composed mainly of the <scene name='78/781973/Gamma/1'> γ (gamma) </scene> protein chain. The axle rotates with three 120° steps, putting the β chains into three different conformations, allowing the ADP and phosphate to bind, the high energy bond to form and the release of ATP.
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'''Q1: Describe how the protein chains are arranged to comprise the F1 region?'''
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'''Q2: What is the role of the axle, explain how it acts on the β subunits?'''
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'''ADP and ATP are bound in the nucleotide binding sites'''
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The F1 shown here has both adenosine diphosphate (ADP) and adenosine triphosphate (ATP) bound in the <scene name='78/781973/Atpandadp/1'>nucleotide binding sites</scene>. See if you can zoom in on the ATP identify the phosphate atoms (orange), sugar moiety and the base moiety. ==>
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The three nucleotide binding sites, primarily located in the β subunits, carry out active ATP synthesis. The sites primarily located in the three α subunits are non-catalytic and exchange bound nucleotide very slowly. They are thought to be a carry over from evolution, and now play a more regulatory role.
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'''Q3: How many phosphates atoms (orange) does ATP have, and how does this differ to ADP?'''
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----
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'''Q4: Between which atoms is the high energy bond formed, and in which location in the ATP synthase does the catalysis occur (which chain)?'''
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'''The F0 region'''
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<scene name='78/781973/F0/1'>The F0</scene> is a circular rotor that is formed of transmembrane α-helices located in the inner mitochondrial membrane. The positively charged hydrogen ions (protons) travel around the circular F0 motor, and turning the F0 rotor in the process, much like a waterwheel. Firstly, the hydrogen ion binds a negatively charged <scene name='78/781973/Aspgluchain/1'>aspartic acid or glutamic acid</scene> residue (amino acid) within the transmembrane α-helices of the F0 motor. This action then allows the F0 to turn, as it can only turn in the hydrophobic membrane when a hydrogen ion is bound to these amino acids, as it neutralises the amino acids negative charge. Secondly, after a full rotation, the hydrogen is removed from the rotor by an <scene name='78/781973/Arg/1'>arginine</scene> amino acid, into a charged pocket, and then is passed to the opposite side of the membrane.
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'''Q5: What is the location and role of the F0 region. How many Transmembrane α-helices are there?'''
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'''Q6: Name two key amino acids, one acidic and one basic, that influence the hydrogen ions's path within the the F0. Which one acts like a broom sweeping the protons off the rotor?'''
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'''Summary'''
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The synthesis of ATP, the cells energy currency, involves a number of steps performed by a tiny molecular motor found in the mitochondrial membrane, called ATP synthase.
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'''Key Terms'''
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ATP = Adenosine triphosphate (nucleotide)
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ADP = Adenosine diphosphate (nucleotide)
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Aspartic acid = An acidic amino acid (negatively charged)
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Glutamic acid = An acidic amino acid (negatively charged)
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Arginine = A basic amino acid (positively charged)
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Transmembrane α-helices = Membrane-spanning α-helices
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ATP synthase = A molecular motor that generates ATP
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Hydrogen ion = A hydrogen atom that has lost (or gained) an electron. A positively charged hydrogen ion is also referred to as a proton
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Moiety = A "part" or "functional group" of a molecule
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You were viewing the molecular model using the Jmol viewer within [http://proteopedia.org/wiki/index.php/Main_Page Proteopedia].
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</StructureSection>
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{{Clear}}
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Current revision

Melanocrtin 4 Receptor complex with peptide (PDB code 6w25)

Drag the structure with the mouse to rotate
MCR1
MCR1

Contents

Melanocortin 1 Receptor: An insight to MCR1 structure, function and regulation

Introduction to MC1R

The highly polymorphic human MC1R gene, located on chromosome 16q24.3 encodes for a MCR1 receptor also known as melanocyte -stimulating hormone receptor. The melanocortin receptor family consists of five members: MC1R, MCR2, MCR3, MC4R and MC5R all of which exhibit functions and are expressed differently (Wolf Horrell, Boulanger and D’Orazio, 2016). The gene is expressed in melanocytes along with other cell types that inhabit the skin such as keratinocytes and fibroblast as well as cells that operate the immune system (Gruis and Doorn, 2012). The activation of the MC1R receptor by ultraviolet radiation increases the production of the dark eumelanin pigment, resulting in the darkening of the skin. MCR1 stimulation also results in increased melanocyte dendricity, proliferation, cell survival and DNA repair. The loss of melanocortin receptor function results in the production of the red/yellow pheomelanin pigment by melanocytes, resulting in the red hair, fair skin, poor tanning, freckling and increased skin cancer risk in humans (Beaumont et al., 2011).

Determination of MC1R Structure

The mature MC1R protein is made up of 317 amino acids and a 7 a-helical transmembrane domain. Based on the sequence similarity analysis, the melanocortin receptor family belong to the class A of G-coupled protein receptors therefore direct information on their secondary and tertiary structures is limited as G coupled protein receptors are resistant to crystallisation (Garcia-Borron, Sanchez-Laorden and Jimenez-Cervantes, 2005) (Zhao and Wu, 2012).

MC4R Ligands

3D structures of MC4R

Updated on 27-January-2022

6w25 – hMC4R + peptide – human
7aue, 7f55, 7f58 – hMC4R in Gs protein complex + nanobody – Cryo EM
7piu – hMC4R in Gs protein complex + nanobody + drug – Cryo EM
7f53, 7piu, 7piv – hMC4R in Gs protein complex + nanobody + a-melanocyte-stimulating hormone – Cryo EM




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Proteopedia Page Contributors and Editors (what is this?)

Alice Clark, Michal Harel

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