The fimbrin and alpha-actinin footprint on actin

satisfying experience in science occurs when information from several areas converge to give a big picture about an important problem. In three papers (Holtz-man et al. in this issue of The Journal of Cell Biology, the disciplines of genetics and structural biology have revealed that two ac-tin cross-linking proteins, fimbrin and alpha-actinin, bind to the same region on actin. Because both proteins belong to a superfamily of actin cross-linking proteins, we have some confidence that other members of the superfamily, including filamin, spectrin, dystrophin, and ABP-120, also bind the same region of actin. This information about binding sites is an important step toward understanding how actin illa-ments are organized by cross-linking proteins into bundles and supramolecular networks. This story is rooted in the classic biochemical studies of muscle proteins. Alpha-actinin was first purified from skeletal muscle (Maruyama and Ebashi, 1965) and characterized as a Z-line component; its rodlike shape was revealed by electron microscopy (see Meyer and Aebi, 1990). Later, spurred by cell biologists who demonstrated that cytoplas-mic extracts of noumuscle cells could undergo reversible sol-gel transformations, a generation of biologists isolated and characterized a number of actin gelation and bundling proteins , including ABP-280 and filamin, speetrin, fascin, and alpha-actinin was rediscovered as a nonmuscle actin cross-linking protein (Burridge and Feramisco, 1981). During the late 1980's, eDNA sequencing showed that many of these gelation factors belonged to a superfamily that shares a common 27-kD NH2-terminal domain (Baron et al., 1987) that binds actin filaments. Fimbrin bundles actin filaments in intestinal brush border microvilli, and it is also located where actin bundles terminate at membrane adhesion plaques (Bretscher and Weber, 1980). The sequence databases (de Arruda et al., 1990) showed that fimbrin was also involved in cell transformation (Lin et al., 1994), and that it was a target of phos-phorylation when leukocytes are activated by growth factors and mitogens (Zu et al., 1990). Hence, fimbrin is also called plastin and pp70. An important structural theme emerged from the sequences: cross-linking proteins in this superfamily are modular, composed of a pair of actin-binding domains, a variable number of spacer domains, and sometimes a cal-modulin-like calcium-binding domain (Matsudaira, 1991). The spacer domains come in two flavors, three-helix bun-dies, and cross-strand beta sheets, and the number of domains determines the length of the cross-link. Both motifs were first predicted by sequence analysis, and the helical nature of the repeats in spectrin was recently …