Sandbox Reserved 471: Difference between revisions
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=Structure= | =Structure= | ||
[[Image:Actin Image.gif]] | |||
Actin exists in both its monomeric (globular, G-actin) and polymeric (filamentous or F-actin) form. The actin monomer is approximately pear shaped. Actin is composed of 376 residues that are folded into two large domains, each comprised of two subdomains. Its secondary structure is 41% helical (22 helices; 153 residues) and 20% beta sheet (20 strands; 77 residues). (PDB) The actin filament is a double-stranded, right-handed helix with a half-pitch of 37 nm and a one-start left-handed genetic helix with a rise of 2.75 nm per monomer. The width of the filament is within the range of 7–10 nm. (Conformational Dynamics of Actin: Effectors and Implications for Biological Function) The large domains are organized to form a hinged molecule with a deep cleft. Subdomains 1 and 3 are structurally related, whereas subdomains 2 and 4 can be viewed as large insertions into subdomains 1 and 3, respectively. There is moderately little contact between the two major domains of actin; the polypeptide chain passes twice between these domains at the loop centered at residue Lys336 and at the linker helix Gln137-Ser145, which functions as the hinge axis between the domains. As a result, two clefts are formed between the domains. Within the upper cleft are the cofactors, an adenine nucleotide and a divalent metal ion, usually magnesium. It is thought that the cofactors interact with the domains on either side, increasing their connectivity. The lower cleft between domains 1 and 3 is lined by residues Tyr143, Ala144, Gly146, Thr148, Gly168, Ile341, Ile345, Leu346, Leu349, Thr351, and Met355, which are predominantly hydrophobic. This cleft constitutes the major binding site for most ABPs, and is thus called the targetbinding or hydrophobic cleft. (Actin Structure and Function). Most of the interaction that occur in the subunit are electrostatic in character but there are also hydrophobic interactions. (Actin Structure and Function) | Actin exists in both its monomeric (globular, G-actin) and polymeric (filamentous or F-actin) form. The actin monomer is approximately pear shaped. Actin is composed of 376 residues that are folded into two large domains, each comprised of two subdomains. Its secondary structure is 41% helical (22 helices; 153 residues) and 20% beta sheet (20 strands; 77 residues). (PDB) The actin filament is a double-stranded, right-handed helix with a half-pitch of 37 nm and a one-start left-handed genetic helix with a rise of 2.75 nm per monomer. The width of the filament is within the range of 7–10 nm. (Conformational Dynamics of Actin: Effectors and Implications for Biological Function) The large domains are organized to form a hinged molecule with a deep cleft. Subdomains 1 and 3 are structurally related, whereas subdomains 2 and 4 can be viewed as large insertions into subdomains 1 and 3, respectively. There is moderately little contact between the two major domains of actin; the polypeptide chain passes twice between these domains at the loop centered at residue Lys336 and at the linker helix Gln137-Ser145, which functions as the hinge axis between the domains. As a result, two clefts are formed between the domains. Within the upper cleft are the cofactors, an adenine nucleotide and a divalent metal ion, usually magnesium. It is thought that the cofactors interact with the domains on either side, increasing their connectivity. The lower cleft between domains 1 and 3 is lined by residues Tyr143, Ala144, Gly146, Thr148, Gly168, Ile341, Ile345, Leu346, Leu349, Thr351, and Met355, which are predominantly hydrophobic. This cleft constitutes the major binding site for most ABPs, and is thus called the targetbinding or hydrophobic cleft. (Actin Structure and Function). Most of the interaction that occur in the subunit are electrostatic in character but there are also hydrophobic interactions. (Actin Structure and Function) | ||
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Polymerization mechanism | Polymerization mechanism | ||
At increased ionic strength, G-actin molecules polymerize into filaments, known as F-actin. F-actin is the main component of the thin filaments in sarcomeres of muscle cells. Muscle sarcomeres use ATP hydrolysis to produce conrtractions by sliding the thin actin filament | At increased ionic strength, G-actin molecules polymerize into filaments, known as F-actin. F-actin is the main component of the thin filaments in sarcomeres of muscle cells. Muscle sarcomeres use ATP hydrolysis to produce conrtractions by sliding the thin actin filament | ||
past thick myosin filaments. The entire process is initiated by the slow formation of actin dimmers and trimers. These serve as a base for filament elongation. During elongation more actin monomers associate to than dissociate from either of the two ends, which results in the net growth of both filament ends. The steady-state phase is characterised by a dynamic equilibrium where the length of the actin filaments remains constant. This means while monomers are associating, other monomers are dissociating from the ends. In this dynamic equilibrium a stationery population of free actin monomers is established and is called the critical concentration. The polarity of the ends of the actin filaments play a key role in elongation. The ends of the filament are referred to as "barbed" and "pointed" according to the polarity of the arrowhead-like structure generated on binding with myosin subfragment 1. ) (Structure and Function of Actin by Wolfgang Kabsch) The barbed or plus end binds actin monomers faster than the pointed or minus end. Although its ATPase activity is not crucial for actin polymerisation, actin self-assembly is associated with the ATPase cycle, which powers this treadmilling process (Conformational Dynamics of Actin: Effectors and Implications for Biological Function) After the actin molecule is changed into a filament, the bound ATP is hydrolysed to ADP and inorganic phosphate is realeased. (Structure and Function of Actin by Wolfgang Kabsch) The formation of the F-actin is what stimulates the actin ATPase. The release of the inorganic phosphate happens more slowly than the formation of the filament so that the growing filament has a cap of ATPactin at its barbed end, while monomers containing ADP and inorganic phosphate accumulate in the rest of the filament. | past thick myosin filaments. The entire process is initiated by the slow formation of actin dimmers and trimers. These serve as a base for filament elongation. During elongation more actin monomers associate to than dissociate from either of the two ends, which results in the net growth of both filament ends. The steady-state phase is characterised by a dynamic equilibrium where the length of the actin filaments remains constant. This means while monomers are associating, other monomers are dissociating from the ends. In this dynamic equilibrium a stationery population of free actin monomers is established and is called the critical concentration. The polarity of the ends of the actin filaments play a key role in elongation. The ends of the filament are referred to as "barbed" and "pointed" according to the polarity of the arrowhead-like structure generated on binding with myosin subfragment 1. ) (Structure and Function of Actin by Wolfgang Kabsch) The barbed or plus end binds actin monomers faster than the pointed or minus end. Although its ATPase activity is not crucial for actin polymerisation, actin self-assembly is associated with the ATPase cycle, which powers this treadmilling process (Conformational Dynamics of Actin: Effectors and Implications for Biological Function) After the actin molecule is changed into a filament, the bound ATP is hydrolysed to ADP and inorganic phosphate is realeased. (Structure and Function of Actin by Wolfgang Kabsch) The formation of the F-actin is what stimulates the actin ATPase. The release of the inorganic phosphate happens more slowly than the formation of the filament so that the growing filament has a cap of ATPactin at its barbed end, while monomers containing ADP and inorganic phosphate accumulate in the rest of the filament. | ||
[[Image:Filament_formation.png]] [[Image:Treadmilling.gif]] | |||
