N. Volkmann et al., An atomic model of actin filaments cross-linked by fimbrin and its implications for bundle assembly and function, J CELL BIOL, 153(5), 2001, pp. 947-956
Actin bundles have profound effects on cellular shape, division, adhesion.
motility. and signaling. Fimbrin belongs to a large family of actin-bundlin
g proteins and is involved in the formation of tightly ordered cross-linked
bundles in the brush border microvilli and in the stereocilia of inner ear
hair cells. Polymorphism in these three-dimensional (3D) bundles has preve
nted the detailed structural characterization required for indepth understa
nding of their morphogenesis and function. Here, we describe the structural
characterization of two-dimensional arrays of actin cross-linked with huma
n T-fimbrin. Structural information obtained by electron microscopy, x-ray
crystallography. and homology modeling allowed us to build the first molecu
lar model for the complete actin-fimbrin cross-link. The restriction of the
arrays to two dimensions allowed us to deduce the spatial relationship bet
ween the components, the mode of fimbrin cross-linking, and the flexibility
within the cross-link. The atomic model of the fimbrin cross-link, the cro
ss-linking rules deduced from the arrays, and the hexagonal packing of acti
n bundles in situ were all combined to generate an atomic model for 3D acti
n-fimbrin bundles. Furthermore, the assembly of the actin-fimbrin arrays su
ggests coupling between actin polymerization, fimbrin binding, and crossbri
dge formation, presumably achieved by a feedback between conformational cha
nges and changes in affinity.