BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 o -100 A per ATP hydrolysis step o Two heads act independently of one another- single stroke then release from actin polymer Can't continuously march along polymer by kinesin Muscle motor protein, transport along transport along microtubules actin fibers Limitations for use in bioengineering applications unidirectional motion AControlling orientation of dable Gand oarO (Vale and Milligan, 2000) Energy source for these molecular motors o AtP hydrolysis cycle linked to conformational change cycle o Energy gained by binding ATP moves kinesin neck linker from rearward-facing position forward to dock against catalytic core of head Motion of one neck pulls other free from previous microtubule binding site and throws it forward to the next site(-80 A) o Origin or directionality: myosin goes opposite direction from kinesin Directionality comes from conformation matching of head to polymers in one direction combined with time sequence of head release from polymer Both motors have an upstroke on binding ATP, downstroke on hydrolysis Kinesin neck docks onto head on upstroke Myosin: tight binding of head to polymer in ATP-free state o Forward motion on upstroke when head releases from polymer inesin: tight binding in ATP-bound state o Reverse motion on downstroke when head releases from polymer Lecture 13-Hybrid macromolecules 6 of 13BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 o ~100 Å per ATP hydrolysis step o Two heads act independently of one another- single stroke then release from actin polymer ƒ Can’t continuously march along polymer by itself Myosin kinesin Muscle motor protein, transport along transport along microtubules actin fibers QuickTime™ and a Video decompressor are needed to see this picture. QuickTime™ and a Video decompressor are needed to see this picture. Limitations for use in bioengineering applications: ¥unidirectional motion ¥Controlling orientation of Ô carÕ cableÕand Ô (Vale and Milligan, 2000) ƒ Energy source for these molecular motors o ATP hydrolysis cycle linked to conformational change cycle o Energy gained by binding ATP moves kinesin neck linker from rearward-facing position forward to dock against catalytic core of head ƒ Motion of one neck pulls other free from previous microtubule binding site and throws it forward to the next site (~80 Å) o Origin or directionality: myosin goes opposite direction from kinesin ƒ Directionality comes from conformation matching of head to polymers in one direction combined with time sequence of head release from polymer ƒ Both motors have an upstroke on binding ATP, downstroke on hydrolysis x Kinesin neck docks onto head on upstroke x Myosin: tight binding of head to polymer in ATP-free state o Forward motion on upstroke when head releases from polymer x Kinesin: tight binding in ATP-bound state o Reverse motion on downstroke when head releases from polymer Lecture 13 – Hybrid macromolecules 6 of 13