BIOL 303 Lecture Notes - Lecture 9: Exergonic Reaction, Treadmilling, Cytotoxic T Cell
Chapter 16 Lecture 2:
• Explain in detail the mechanisms governing actin polymerization and treadmilling Actin
Nucleation (4-9).
▪ Nucleation is the Rate-Limiting Step in the Formation of Actin Filaments.
• Nucleus in this case means a “collection” of actin subunits.
• Initial aggregate of stabilized actin subunits = nucleus.
▪ Nucleation imparts a kinetic barrier to actin polymerization, creating an
initial delay, followed by rapid growth once nucleation is achieved, termed
elongation.
▪ Once local subunits reach a Critical Concentration (Cc), subunit addition
exactly balances subunit subtraction = steady state.
o Actin Subunit Critical Concentration Determines Dissociation Rate
▪ Critical concentration (Cc) = dissociation constant (Kd) = Koff/Kon
o Actin filaments have two distinct ends that grow at different rates
▪ Kon and Koff are much greater at the plus end of actin filaments, so
polymerization and depolymerization occur at the plus end faster than the
minus end.
▪ When the number of free actin subunits exceeds the Cc, the chance in
Gibson free Energy (∆G) is negative (Energy Reactants > Energy
Products), and thus subunits can polymerize spontaneously. (Exergonic
reaction).
▪ The exergonic reaction can fuel rearrangements of the cell surface
through actin polymerization without the need for another energy source.
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o ATP Hydrolysis Within Actin Filaments Leads to Treadmilling at Steady State.
▪ Actin can hydrolyze ATP, but this process is slow in free G-actin,
hydrolysis speeds up in F-actin – So most monomers have ATP.
• After hydrolysis, ADP remains trapped in polymer.
• So, two forms of actin filaments can exist: one with ATP bound
(T-form), and one with ADP bound (D-form).
▪ Energy from ATP to ADP hydrolysis is mostly stored in actin polymer.
• So ∆G is more negative (more exergonic) when a D form polymer
dissociates vs when T form dissociates.
▪ Consequently Kon/Koff (aka Cc) for D-form is larger than T-form (i.e. more
energetically favorable to dissociate).
• So, at some concentrations of free subunits, D-form polymers will
shrink while T-form polymers grow, Cc(D) > Cc (T)
▪ When rate of addition of actin subunits (remember mostly T-form) is
faster than ATP hydrolysis at plus end, but slower than hydrolysis at
minus end, actin filament treadmilling occurs.
▪ Simultaneous addition at plus end and loss and minus end = No net change
in filament length.
Chapter 16 Part II:
• Explain in detail the mechanisms governing actin polymerization and treadmilling (slides
4-5).
o See 16 part I
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Document Summary
Chapter 16 lecture 2: explain in detail the mechanisms governing actin polymerization and treadmilling actin. Nucleation (4-9): nucleation is the rate-limiting step in the formation of actin filaments, nucleus in this case means a collection of actin subunits. Gibson free energy ( g) is negative (energy reactants > energy. Chapter 16 part ii: explain in detail the mechanisms governing actin polymerization and treadmilling (slides. Activated receptors bind adaptor proteins which bind caspases once bound they form heterodimers, cleave partner caspase (1 large & 1 small subunit) to form active complex activate executioner caspases: executioner caspases: normally inactive dimers. Can now catalyze protein cleavage events that will kill cell: recall what cad proteins do and how they relate to tunel labeling (slide 7), cad cleaves chromosomal dna in between nucleosomes. This then unfolds and forms a wheel-like heptamer called an apoptosome: casp9: recruited by the apoptosome and activates executioner caspases, bcl2: responsible for anti-apoptotic.
