In brief

Electron microscopy performed by Melby et al. (page 1595) provides new clues as to how structural maintenance of chromosomes (SMC) proteins might help in two enormous tasks: chromosome condensation and sister chromatid cohesion. The primary structure of the SMCs provides a problem. The two motifs that constitute the putative ATP-binding site are located at opposite ends of the molecule, separated by a long coiled coil, an intervening stretch, and another coiled coil. If the coiled coil is aligned, these motifs could come together in three-dimensional space in one of two ways: the intervening sequence could act as a hinge, allowing the two ends of the molecule to fold back onto each other, or the SMC dimer could form in an antiparallel fashion. Melby et al. find that both of these possibilities occur. Functional studies of SMCs have focused largely on yeast and Xenopus proteins, but Melby et al. look at MukB from Escherichia coli and BsSMC from Bacillus subtilus . As in a previous study, MukB appeared primarily as a large and small globule separated by a thin rod. In the earlier interpretation, the rod was identified as a single parallel coiled coil. But lighter shadowing and differing sample preparation allow Melby et al. to observe rarer forms of the protein, in which the rod is split in two, or even opened into a V shape. This suggests that the rod is made from two coiled coils, folded back on each other. A fibronectin domain added to one end of a modified protein appears at both ends of the V-shaped dimer, indicating that each half of the V is an antiparallel coiled coil, z 300 amino acids in length. This far exceeds the previous record for antiparallel coiled coils of 35–45 amino acids. It is unclear how these long, antiparallel coiled coils are stabilized. The new data suggest a symmetrical structure. “All the previous thinking has been that this is a polar molecule with DNA binding at one end and a motor at the other,” says senior author Harold Erickson. “Now both ends have complete and identical functional domains. If this thing is moving along DNA, both ends could be translocating the DNA simultaneously.” Without any proof of motor activity or data on SMC conformation and flexibility in vivo, mechanistic theories are still pure speculation. A Xenopus complex that includes SMC proteins can introduce supercoils into DNA; this could be achieved by two SMC-based motors moving along one groove of the DNA in opposite directions, or by SMC arms wrapping DNA around a core particle. As for sister chromatid cohesion, the extended form of an SMC could reach for up to 100 nm, with an active binding site at each end. “These molecules might act as a bridge,” says Erickson. “It might really be making use of the length.” Sorting by a Phosphatase