3HH3 module 1 lecture 3-post

3HH3 module 1 lecture 3-post - A ctin filament formation

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Bio 3HH3 2010 2 Regulation of AF polymerization: The filament assembles from actin monomers Figure 16-12 Molecular Biology of the Cell (© Garland Science 2008) ATP-binding pocket
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http://www.ncbi.nlm.nih.gov/books/NBK21594/figure/A5147/?report=objectonly ... and movie. Actin polymerization can be divided into three steps
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Nucleation often occurs at the plasma membrane: All actin filaments are labelled with phalloidin (green). The cell was incubated with rhodamine-labelled actin for 5 minutes prior to fixation to reveal newly-formed actin. MboC Fourth edition http://www.ncbi.nlm.nih.gov/books/NBK26809/figure/A3004/?report=objectonly Cell cortex
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Bio 3HH3 2010 5 The structures of Arp2/3 are very similar to actin monomer Figure 16-34a Molecular Biology of the Cell (© Garland Science 2008) Nucleation: The Arp2/3 complex can nucleate actin polymerization. The two actin-like subunits serve as a template for mononer addition by mimicking the minus of a growing actin filament
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Bio 3HH3 2010 6 Figure 16-34b Molecular Biology of the Cell (© Garland Science 2008) Nucleation of actin filament occurs at the minus end allowing elongation at the plus end Plus end is also called the barbed end ATP- binding
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Bio 3HH3 2010 7 Filament branching is the result of ARP complex bound to the side of a preexisting AF. Branching occurs at 70 o angle and has a treelike web. Figure 16-34 Molecular Biology of the Cell (© Garland Science 2008)
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Bio 3HH3 2010 8 Isolated Arp2/3 complexes do not efficiently nucleate AF assembly. However binding of the complexes to the side of a pre-existing “mother” filament rapidly activates nucleation. Daughter branches detach (debranch) from the mother filament to initiate new assembly. One possible model modified from: Kover, Nature Cell Biology 2006, 8, 783-785
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Bio 3HH3 2010 9 Nucleation: Formin is another actin nucleating protein Protein dimer with an FH2 domain that binds actin Hoop-shaped structure that acts like a plus-end filament cap Filament elongation occurs through insertion of actin monomers between the formin cap and the plus end of the filament so formin moves with the growing plus-end!
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Bio 3HH3 2010 10 Xu et al., Cell 2004, vol. 116, 711-723
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Bio 3HH3 2010 11 Xu et al., Cell 2004, vol. 116, 711-723 Model for insertion of actin monomers between the formin cap and the plus end of the filament
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3HH3 module 1 lecture 3-post - A ctin filament formation

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