Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

938 Chapter 16: The Cytoskeleton
(A)
N
(B)
tail
stalk
attachment to
another microtubule
(C)
tail AAA domains stalk AAA domains
microtubule
attached to stalk
ADP
+
P i
power stroke,
8 nm
AAA domains
in motor head
major ATPase
C-terminal domain
15 nm
C
Figure 16–59 The power stroke of
dynein. (A) The organization of the
domains in each dynein heavy chain. This
is a huge polypeptide, containing nearly
4000 amino acids. The number of heavy
chains in a dynein is equal to its number
of motor heads. (B) Illustration of dynein
c, a monomeric axonemal dynein found in
the unicellular green alga Chlamydomonas
reinhardtii. The large dynein motor head
is a planar ring containing a C-terminal
domain (gray) and six AAA domains, four
of which retain ATP-binding sequences,
but only one of which (dark red) has the
major ATPase activity. Extending from
the head are a long, coiled-coil stalk with
the microtubule-binding site at the tip,
and a tail that attaches to an adjacent
microtubule in the axoneme. In the ATPbound
state, the stalk is detached from
the microtubule, but ATP hydrolysis
causes stalk–microtubule attachment (left).
Subsequent release of ADP and phosphate
(P i ) then leads to a large conformational
“power stroke” involving rotation of the
head and stalk relative to the tail (right).
Each cycle generates a step of about 8 nm,
thereby contributing to flagellar beating (see
Figure 16–65). In the case of cytoplasmic
dynein, the tail is attached to a cargo such
as a vesicle, and a single power stroke
transports the cargo about 8-nm along
the microtubule toward its minus end (see
Figure 16–60). (C) Electron micrographs of
purified monomeric dyneins in two different
conformations representing different steps
in the mechanochemical cycle. (C, from
S.A. Burgess et al., Nature 421:715–718,
2003. With permission from Macmillan
Publishers Ltd.)
Dyneins are the largest of the known molecular motors, and they are also
among the fastest: axonemal dyneins attached to a glass slide can move microtubules
at the rate of 14 MBoC6 μm/sec. m16.64/16.59 The dynein motor is structurally unrelated to
myosins and kinesins, but still follows the general rule of coupling nucleotide
hydrolysis to microtubule binding and unbinding as well as to a force-generating
conformational change (Figure 16–59).
Microtubules and Motors Move Organelles and Vesicles
A major function of cytoskeletal motors in interphase cells is the transport and
positioning of membrane-enclosed organelles (Movie 16.10). Kinesin was originally
identified as the protein responsible for fast anterograde axonal transport,
the rapid movement of mitochondria, secretory vesicle precursors, and various
synapse components down the microtubule highways of the axon to the distant
nerve terminals. Cytoplasmic dynein was identified as the motor responsible for
transport in the opposite direction, retrograde axonal transport. Although organelles
in most cells need not cover such long distances, their polarized transport
is equally necessary. A typical microtubule array in an interphase cell is oriented
with the minus ends near the center of the cell at the centrosome and the plus
ends extending to the cell periphery. Thus, centripetal movements of organelles
or vesicles toward the cell center require the action of minus-end directed cytoplasmic
dynein motors, whereas centrifugal movements toward the periphery
require plus-end directed kinesin motors. Interestingly, in animal cells, nearly all
minus-end directed transport is driven by the single cytoplasmic dynein 1 motor,
whereas 15 different kinesins are used for plus-end directed transport.