User:Andy Maloney/Notebook/Lab Notebook of Andy Maloney/2009/09/01/Kinesin Motor Mechanics: Binding, Stepping, Tracking, Gating, and Limping Review
This is my review of the following paper. Please do not use my review as a reference. If I incorrectly state something, please correct it on the talk page.
Block talks about a meeting he attended at the 10th Biophysical Discussions meeting. There they apparently talked about kinesin and the paper is a result of the discussions.
Does kinesin take sub-steps?
There is no consensus on if kinesin takes sub-steps. Block did reference a paper by Yanagida where they talk about how force velocity curves implies the existence of sub-steps.
Block does think sub-steps can exist. It is just that there has been no conclusive evidence to support them. I think he does now because of this paper but, I have to reread that one.
Kinesin's walking pattern
Gelles' group describes the different proposed walking methods of kinesin. Right now the literature and most prominent scientists believe kinesin walks "hand over hand" .... foot over foot in an asymmetric way.
For kinesin to walk, the chemical cycles that hydrolyze ATP in its feet must be out of phase with each other. I really need to think about this more because I'm not very clear on this. Right now there are two ideas behind this.
- Gated rear head mechanism
- Release of the trailing foot is accelerated by internal strain. Reference
- Gated front head mechanism
- ATP binding to the front foot is suppressed through strain. Reference
Other things of merit that require "out of phase" motion include kinesin stepping backwards. Ishiwata's group showed that there was a 7 fold weakening of the KD for kinesin to put a foot in the backward direction.
Also, Block talks about another paper of his where they used non-hydrolyzable ATP analogs (AMP-PNP) to prevent forward motion. What they saw was that the AMP-PNP caused long pauses for kinesin motion and when it did start moving again, it required a step backwards to move forward again. He used this bit of knowledge to say that it is ATP binding that causes a power stroke and not necessarily that the neck linker has to bind to the microtubule to cause a power stroke. I need to look at crystal structures of kinesin.
So far there are 3 contenders.
- There is a release of stored strain when the trailing foot unbinds from the microtubule. This then permits the leading foot to make a power stroke.
- ATP binding induces the neck linker to dock on the leading foot. This produces motion of the trailing foot.
- Binding of ATP is load dependent. This indicates that when ATP binds to a foot, it causes the step.
No one really knows if when a kinesin takes a step back, it is a true reversal of motion chemically and physically.
- Both feet of the kinesin like to be on the microtubule. Makes sense if processivity is to work.
- The neck linker of kinesin is ~11-13 amino acids long.
- No one knows if a kinesin walks on one protofilament, or between two protofilaments.
To fill in later...