Transcript Kinesin

KINESIN
SARA VAN NORTWICK
GEOMETRIC COMPUTATIONS IN MOLECULAR BIOLOGY
SS 2007
ETH
THE STRUCTURE
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X-ray crystallography by
Kull et al. (1996)
 Resolution
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Dimer
= 1.8 A
LET’S MOTOR!
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The Family of Motor Proteins
Large and varied responsibilities
 Unidirectional movement
 Fuel = ATP
 Share motor “head” domain (structural core,
common ancestor)
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WHERE ARE WE GOING AND WHY?
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Center
Periphery
Compass = Microtubule Polarity
 Anterograde Transport (towards the positive)
Point A to Point B
 Kinesin > Diffusion
Alignment
 Mitosis (cell division)
HOW FAST ARE WE TALKING?
2 um/sec
 8 nm per step (spacing of tubulin dimers along the microtubule)
 = 250 steps/second!
 Protein head = 7.5 X 4.5 X 4.5 nm
 ≈ speed and thrust of the supersonic car
 60% efficiency
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THE MOTOR IN ACTION
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Kinesin Movement Video:
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http://www.scripps.edu/cb/milligan/research/movies/kinesin_mov.html
MANY VARIETIES…
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Motor domain conserved @ N-terminus
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40 known variations in Humans
Differences in adaptor structure between motor
and the object to be moved
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BREAKING IT DOWN
Two heavy
chains
comprise
globular head
•
Light
Chains
comprise
cargo binding
region
•
KINESIN VS. MYOSIN
Motor domain is
similar in both
motor proteins
Very little amino
acid similarity
Kinesin is 340 aa
while myosin is
850 aa
RMS of 3.5 A for
183 aa of kinesin
motor domain
STRUCTURE ISN’T ALWAYS ENOGUH…
REFERENCES
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Kozeilski, Sack, et al. The Crystal Structure of Dimeric
Kinesin and Implication fo Microtubule-Dependent
Motility. Cell, Vol 91, 985-994. December, 26, 1997.
Molecular Biology of the Cell
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.figgrp
.3054
PDB Molecule of the Month
Kull, Sablin, et al.(1996). Crystal structure of the kinesin
motor domains reveals a structural similarity to myosin.
Nature 380, 550-554.
Wikipedia
Block, Steve. Kinesin: What Gives? Cell, Vol 93 5-8. April,
1998.
WE’VE ARRIVED…
Questions?