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

ACTIN AND ACTIN-BINDING PROTEINS
899
plus end
actin molecule
plus end
NH 2
HOOC
37 nm
ATP
(ADP when
in filament)
minus end
minus end
(A)
accessory proteins cross-link and bundle the filaments together, making largescale
actin structures that are much more rigid than an individual actin filament.
Nucleation Is the Rate-Limiting Step in the Formation of Actin
Filaments
The regulation of actin filament formation is an important mechanism by which
cells control their shape and movement. Small oligomers of actin subunits can
MBoC6 m16.12/16.11
assemble spontaneously, but they are unstable and disassemble readily because
each monomer is bound to only one or two other monomers. For a new actin filament
to form, subunits must assemble into an initial aggregate, or nucleus, that is
stabilized by multiple subunit–subunit contacts and can then elongate rapidly by
addition of more subunits. This process is called filament nucleation.
Many features of actin nucleation and polymerization have been studied with
purified actin in a test tube (Figure 16–13). The instability of smaller actin aggregates
creates a kinetic barrier to nucleation. When polymerization is initiated, this
barrier results in a lag phase during which no filaments are observed. During this
lag phase, however, a few of the small, unstable aggregates succeed in making the
transition to a more stable form that resembles an actin filament. This leads to a
plus
end
minus
end
(B)
(C)
25 nm
Figure 16–11 The structures of an actin
monomer and actin filament. (A) The
actin monomer has a nucleotide (either
ATP or ADP) bound in a deep cleft in the
center of the molecule. (B) Arrangement
of monomers in a filament consisting
of two protofilaments, held together by
lateral contacts, which wind around each
other as two parallel strands of a helix,
with a twist repeating every 37 nm. All the
subunits within the filament have the same
orientation. (C) Electron micrograph of
negatively stained actin filament.
(C, courtesy of Roger Craig.)
(A)
0.5 µm
barbed
(plus) end
(B)
pointed
(minus) end
20 nm
Figure 16–12 Structural polarity of the
actin filament. (A) This electron micrograph
shows an actin filament polymerized from a
short actin filament seed that was decorated
with myosin motor domains, resulting in an
arrowhead pattern. The filament has grown
much faster at the barbed (plus) end than at
the pointed (minus) end. (B) Enlarged image
and model showing the arrowhead pattern.
(A, courtesy of Tom Pollard; B, adapted
from M. Whittaker, B.O. Carragher and
K.A. Milligan, Ultramicro. 54:245–260, 1995.)