Limits...
The cohesin complex: sequence homologies, interaction networks and shared motifs.

Jones S, Sgouros J - Genome Biol. (2001)

Bottom Line: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex.We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs.The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computational Genome Analysis Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK. Susan.Jones@icrf.icnet.uk

ABSTRACT

Background: Cohesin is a macromolecular complex that links sister chromatids together at the metaphase plate during mitosis. The links are formed during DNA replication and destroyed during the metaphase-to-anaphase transition. In budding yeast, the 14S cohesin complex comprises at least two classes of SMC (structural maintenance of chromosomes) proteins - Smc1 and Smc3 - and two SCC (sister-chromatid cohesion) proteins - Scc1 and Scc3. The exact function of these proteins is unknown.

Results: Searches of protein sequence databases have revealed new homologs of cohesin proteins. In mouse, Mmip1 (Mad member interacting protein 1) and Smc3 share 99% sequence identity and are products of the same gene. A phylogenetic tree of SMC homologs reveals five families: Smc1, Smc2, Smc3, Smc4 and an ancestral family that includes the sequences from the Archaea and Eubacteria. This ancestral family also includes sequences from eukaryotes. A cohesion interaction network, comprising 17 proteins, has been constructed using two proteomic databases. Genes encoding six proteins in the cohesion network share a common upstream region that includes the MluI cell-cycle box (MCB) element. Pairs of the proteins in this network share common sequence motifs that could represent common structural features such as binding sites. Scc2 shares a motif with Chk1 (kinase checkpoint protein), that comprises part of the serine/threonine protein kinase motif, including the active-site residue.

Conclusions: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex. We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs. The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

Show MeSH
Structure of an SMC protein. (a) The five domains of SMC proteins. The amino-terminal domain includes a Walker A motif and the carboxy-terminal domain a DA-box (also known as a Walker B motif). (b) Proposed dimeric interaction of SMC molecules (see, for example, [8]).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC30708&req=5

Figure 1: Structure of an SMC protein. (a) The five domains of SMC proteins. The amino-terminal domain includes a Walker A motif and the carboxy-terminal domain a DA-box (also known as a Walker B motif). (b) Proposed dimeric interaction of SMC molecules (see, for example, [8]).

Mentions: The Smc1 and Smc3 proteins belong to the conserved and well characterized SMC family, which also includes Smc2 and Smc4, components of the condensin macromolecular complex. The SMCs have a highly conserved structure comprising five domains arranged in a head-rod-tail architecture, including a Walker A motif in the amino-terminal domain and a DA-box (Walker B motif) in the carboxy-terminal domain (Figure 1a) [5,6,7]. Dimeric models of Smc1-Smc3 protein complexes have been proposed, in which the coiled-coil domains of each protomer interact in an antiparallel arrangement, bringing the Walker A and B motifs together at the termini of the structure, forming two complete ATP-binding sites (Figure 1b) [7,8,9,10,11]. In accordance with this model, an SMC homodimer has been observed by electron microscopy in Bacillus subtilis [8]. A similar model is proposed for Smc1-Smc3 heterodimers in eukaryotes [7].


The cohesin complex: sequence homologies, interaction networks and shared motifs.

Jones S, Sgouros J - Genome Biol. (2001)

Structure of an SMC protein. (a) The five domains of SMC proteins. The amino-terminal domain includes a Walker A motif and the carboxy-terminal domain a DA-box (also known as a Walker B motif). (b) Proposed dimeric interaction of SMC molecules (see, for example, [8]).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC30708&req=5

Figure 1: Structure of an SMC protein. (a) The five domains of SMC proteins. The amino-terminal domain includes a Walker A motif and the carboxy-terminal domain a DA-box (also known as a Walker B motif). (b) Proposed dimeric interaction of SMC molecules (see, for example, [8]).
Mentions: The Smc1 and Smc3 proteins belong to the conserved and well characterized SMC family, which also includes Smc2 and Smc4, components of the condensin macromolecular complex. The SMCs have a highly conserved structure comprising five domains arranged in a head-rod-tail architecture, including a Walker A motif in the amino-terminal domain and a DA-box (Walker B motif) in the carboxy-terminal domain (Figure 1a) [5,6,7]. Dimeric models of Smc1-Smc3 protein complexes have been proposed, in which the coiled-coil domains of each protomer interact in an antiparallel arrangement, bringing the Walker A and B motifs together at the termini of the structure, forming two complete ATP-binding sites (Figure 1b) [7,8,9,10,11]. In accordance with this model, an SMC homodimer has been observed by electron microscopy in Bacillus subtilis [8]. A similar model is proposed for Smc1-Smc3 heterodimers in eukaryotes [7].

Bottom Line: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex.We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs.The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

View Article: PubMed Central - HTML - PubMed

Affiliation: Computational Genome Analysis Laboratory, Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK. Susan.Jones@icrf.icnet.uk

ABSTRACT

Background: Cohesin is a macromolecular complex that links sister chromatids together at the metaphase plate during mitosis. The links are formed during DNA replication and destroyed during the metaphase-to-anaphase transition. In budding yeast, the 14S cohesin complex comprises at least two classes of SMC (structural maintenance of chromosomes) proteins - Smc1 and Smc3 - and two SCC (sister-chromatid cohesion) proteins - Scc1 and Scc3. The exact function of these proteins is unknown.

Results: Searches of protein sequence databases have revealed new homologs of cohesin proteins. In mouse, Mmip1 (Mad member interacting protein 1) and Smc3 share 99% sequence identity and are products of the same gene. A phylogenetic tree of SMC homologs reveals five families: Smc1, Smc2, Smc3, Smc4 and an ancestral family that includes the sequences from the Archaea and Eubacteria. This ancestral family also includes sequences from eukaryotes. A cohesion interaction network, comprising 17 proteins, has been constructed using two proteomic databases. Genes encoding six proteins in the cohesion network share a common upstream region that includes the MluI cell-cycle box (MCB) element. Pairs of the proteins in this network share common sequence motifs that could represent common structural features such as binding sites. Scc2 shares a motif with Chk1 (kinase checkpoint protein), that comprises part of the serine/threonine protein kinase motif, including the active-site residue.

Conclusions: We have combined genomic and proteomic data into a comprehensive network of information to reach a better understanding of the function of the cohesin complex. We have identified new SMC homologs, created a new SMC phylogeny and identified shared DNA and protein motifs. The potential for Scc2 to function as a kinase - a hypothesis that needs to be verified experimentally - could provide further evidence for the regulation of sister-chromatid cohesion by phosphorylation mechanisms, which are currently poorly understood.

Show MeSH