SMC protein

Eukaryotes have at least six SMC proteins in individual organisms, and they form three distinct heterodimers with specialized functions:

• A pair of SMC1 and SMC3 constitutes the core subunits of the cohesin complexes involved in sister chromatid cohesion.[4][5][6] SMC1 and SMC3 also have functions in the repair of DNA double-strained breaks in the process of homologous recombination.[7]
• Likewise, a pair of SMC2 and SMC4 acts as the core of the condensin complexes implicated in chromosome condensation.[8][9] SMC2 and SMC4 have the function of DNA repair as well. Condensin I plays a role in single-strained break repair but not in double-strained breaks. The opposite is true for Condensin II, which plays a role in homologous recombination.[7]
• A dimer composed of SMC5 and SMC6 functions as part of a yet-to-be-named complex implicated in DNA repair and checkpoint responses.[10]

Each complex contains a distinct set of non-SMC regulatory subunits. Some organisms have variants of SMC proteins. For instance, mammals have a meiosis-specific variant of SMC1, known as SMC1β.[11] The nematode Caenorhabditis elegans has an SMC4-variant that has a specialized role in dosage compensation.[12]

The following table shows the SMC proteins names for several model organisms and vertebrates:[13]

SMC proteins are conserved from bacteria to humans.[14][15] Most bacteria have a single SMC protein in individual species that forms a homodimer.[16][17] Recently SMC proteins have been shown to aid the daughter cells DNA at the origin of replication to guarantee proper segregation. In a subclass of Gram-negative bacteria, including Escherichia coli, a distantly related protein known as MukB plays an equivalent role.[18]

SMC proteins are 1,000-1,500 amino-acid long. They have a modular structure that is composed of the following domains:

1. Walker A ATP-binding motif
2. coiled-coil region I
3. hinge region
4. coiled-coil region II
5. Walker B ATP-binding motif; signature motif

SMC dimers form a V-shaped molecule with two long coiled-coil arms.[19][20] To make such a unique structure, an SMC protomer is self-folded through anti-parallel coiled-coil interactions, forming a rod-shaped molecule. At one end of the molecule, the N-terminal and C-terminal domains form an ATP-binding domain. The other end is called a hinge domain. Two protomers then dimerize through their hinge domains and assemble a V-shaped dimer.[21][22] The length of the coiled-coil arms is ~50 nm long. Such long "antiparallel" coiled coils are very rare and found only among SMC proteins (and their relatives such as Rad50). The ATP-binding domain of SMC proteins is structurally related to that of ABC transporters, a large family of transmembrane proteins that actively transport small molecules across cellular membranes. It is thought that the cycle of ATP binding and hydrolysis modulates the cycle of closing and opening of the V-shaped molecule. Still, the detailed mechanisms of action of SMC proteins remain to be determined.

The SMC proteins have the potential to form a larger ring-like structure. The ability to create different architectural arrangements allows for various regulations of functions. Some of the possible configurations are double rings, filaments, and rosettes. Double rings are 4 SMC proteins bound at the heads and hinge, forming a ring. Filaments are a chain of alternating SMCs. Rosettes are rose-like structures with terminal segments in the inner region and hinge in the outer region.[23]