SMC proteins are conserved from bacteria to humans. Most bacteria have a single SMC protein in individual species that forms a homodimer. In a subclass of Gram-negative bacteria including Escherichia coli, a distantly related protein known as MukB plays an equivalent role.
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.
- Likewise, a pair of SMC2 and SMC4 acts as the core of the condensin complexes implicated in chromosome condensation.
- A dimer composed of SMC5 and SMC6 functions as part of a yet-to-be-named octameric complex implicated in DNA repair and checkpoint responses.
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. The nematode Caenorhabditis elegans has an SMC4-variant that has a specialized role in dosage compensation.
SMC protein monomers have a modular structure and contain 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
SMC dimers form a V-shaped molecule with two long coiled-coil arms, each having an ATP-binding domain at its distal end. 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, but the detailed mechanisms of action of SMC proteins remain to be determined.
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