SMC complexes represent a large family of

ATPases ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...

that participate in many aspects of higher-order chromosome organization and dynamics. SMC stands for Structural Maintenance of Chromosomes.

Classification

Eukaryotic SMCs

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 Cohesin is a protein complex that mediates sister chromatid cohesion, homologous recombination, and DNA looping. Cohesin is formed of SMC3, SMC1, SCC1 and SCC3 ( SA1 or SA2 in humans). Cohesin holds sister chromatids together after DNA rep ...

complexes involved in sister chromatid cohesion. * Likewise, a pair of SMC2 and SMC4 acts as the core of the

condensin Condensins are large protein complexes that play a central role in chromosome assembly and segregation during mitosis and meiosis (Figure 1). Their subunits were originally identified as major components of mitotic chromosomes assembled in ''Xeno ...

complexes implicated in chromosome condensation. * A dimer composed of SMC5 and SMC6 functions as part of a yet-to-be-named complex implicated in

DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...

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 Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately resu ...

-specific variant of SMC1, known as SMC1β. The nematode ''

Caenorhabditis elegans ''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a blend of the Greek ''caeno-'' (recent), ''rhabditis'' (ro ...

'' has an SMC4-variant that has a specialized role in

dosage compensation Dosage compensation is the process by which organisms equalize the expression of genes between members of different biological sexes. Across species, different sexes are often characterized by different types and numbers of sex chromosomes. In order ...

Prokaryotic SMCs

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 Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

bacteria including ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

'', a distantly related protein known as MukB plays an equivalent role.

Molecular structure

Primary structure

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

Walker A Walker or The Walker may refer to: People *Walker (given name) *Walker (surname) * Walker (Brazilian footballer) (born 1982), Brazilian footballer Places In the United States *Walker, Arizona, in Yavapai County *Walker, Mono County, California ...

ATP-binding motif An ATP-binding motif is a 250-residue sequence within an ATP-binding protein’s primary structure. The binding motif is associated with a protein’s structure and/or function. ATP is a molecule of energy, and can be a coenzyme, involved in a num ...

coiled-coil A coiled coil is a structural motif in proteins in which 2–7 alpha helix, alpha-helices are coiled together like the strands of a rope. (Protein dimer, Dimers and Protein trimer, trimers are the most common types.) Many coiled coil-type protei ...

region I # hinge region # coiled-coil region II # Walker B ATP-binding motif; signature motif

Secondary and tertiary structure

SMC dimers form a V-shaped molecule with two long

arms. To make such a unique structure, an SMC protomer is self-folded through anti-parallel

interactions, forming a rod-shaped molecule. At one end of the molecule, the N-terminal and C-terminal domains together 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. 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 its relatives such as Rad50). The ATP-binding domain of SMC proteins is structurally related to that of

ABC transporters The ATP synthase, ATP-binding cassette transporters (ABC transporters) are a transport system superfamily that is one of the largest and possibly one of the oldest gene family, gene families. It is represented in all extant taxon, extant Phylum ...

, 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 Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

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.

Genes

The following human genes encode SMC proteins: *

SMC1A Structural maintenance of chromosomes protein 1A (SMC1A) is a protein that in humans is encoded by the ''SMC1A'' gene. SMC1A is a subunit of the cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. ...

SMC1B Structural maintenance of chromosomes protein 1B (SMC-1B) is a protein that in humans is encoded by the ''SMC1B'' gene. SMC-1B belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis. SMC1ß ...

SMC2 Structural maintenance of chromosomes protein 2 (SMC-2) also known as chromosome-associated protein E (CAP-E) is a protein that in humans is encoded by the ''SMC2'' gene. SMC-2 is a subunit of condensin I and II, large protein complexes involved ...

SMC3 Structural maintenance of chromosomes protein 3 (SMC3) is a protein that in humans is encoded by the SMC3 gene. SMC3 is a subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. Cohesi ...

SMC4 Structural maintenance of chromosomes protein 4 (SMC-4) also known as chromosome-associated polypeptide C (CAP-C) or XCAP-C homolog is a protein that in humans is encoded by the ''SMC4'' gene. SMC-4 is a core subunit of condensin Condensins are la ...

SMC5 Structural maintenance of chromosomes protein 5 is a protein encoded by the ''SMC5'' gene in human. The structural maintenance of chromosomes' complex underlying mechanisms involved in the dynamics of chromatin dynamics is unknown, and new discove ...

SMC6 Structural maintenance of chromosomes protein 6 is a protein that in humans is encoded by the ''SMC6'' gene. Structure The SMC6 was discovered first in fission yeast as RAD18 (SMC6). It forms a heterodimeric complex with Spr18 (SMC5) protein. In ...

References

{{Portal bar, Biology, border=no EC 3.6.3 Cell biology Mitosis Cell cycle