Michael Eck
Dana-Farber Cancer Institute and Harvard Medical School
Abstract:
Formin proteins
participate in a wide range of cytoskeletal processes that are required
for cell polarity, cytokinesis, and morphogenesis in all eukaryotes.
The defining feature of formin proteins is a highly conserved ~400
residue region, the Formin Homology–2 (FH2) domain, which has recently
been found to nucleate actin filaments. Unlike the Arp2/3 complex,
which nucleates branched filaments, formins induce unbranched filaments
required for formation of diverse actin-containing structures. Here we
report the crystal structure of the S. cerevesiae Bni1p FH2
domain. The mostly a-helical FH2 domain forms a ring-shaped homodimer in which the two subunits are
tied together in a head-to-tail arrangement by a unique “lasso”
structure. The reciprocal tethering provided by the lasso and an
adjacent linker segment in each molecule creates a stable, yet flexible
dimer. Conserved patches on one surface of the FH2 dimer are likely
sites of interaction with actin. The unusual tethered-dimer
architecture of the FH2 domain may allow formins to nucleate actin
filaments by stabilizing two actin subunits in the helical orientation
found at the barbed end of actin filaments, and to stair-step on the
barbed end of the nascent filament as it grows.
2008 Run
Nov 19th - Dec 22nd
