PROSITE documentation PDOC52065MCM10 internal and C-terminal domains (MCM-ID and MCM-CTD) profiles
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Eukaryotic DNA replication is carried out by large multiprotein machines that coordinate DNA unwinding and synthesis at the replication fork. Minichromosome Maintenance protein 10 (MCM10) is exclusive to eukaryotes and is essential to both initiation and elongation phases of chromosomal DNA replication. MCM10 works as scaffold protein that can interact with many proteins, such as DNA polymerase α (pol α) and DNA primase, some subunits of Cdc45-Mcm2-7-GINS helicase (CMG) complex, and PCNA. In addition, MCM10 binds both single-stranded (ss) and double-stranded (ds) DNA. MCM10 does not have a preference for particular DNA sequences or topological structures, but its affinity for ssDNA is higher than for dsDNA [1,2,3,4,5].
MCM10 is composed of three domains, the N-terminal (NTD), internal (ID), and C-terminal (CTD) domains, each containing distinct functional regions involved in DNA binding and/or protein-protein contacts. The structural integrity of ID and CTD is dependent on the presence of bound zinc [1,2,3,4,5].
The NTD is common among MCM10 proteins from yeast to humans, but is not essential and less well conserved than the central ID. Functionally, the NTD contributes to self-oligomerization and partner protein interaction. A conserved coiled-coil (CC) within the NTD is responsible for MCM10 self-interaction [4].
The ID is the most highly conserved region of MCM10 and mediates both protein-DNA and protein-protein interactions. The MCM10-ID is composed of an oligonucleotide/oligosaccharide binding (OB)-fold followed in tandem by a variant and highly basic CCCH-type zinc finger (ZnF1), which form a unified DNA binding platform capable of binding ss- and dsDNA (see <PDB:3EBE>). DNA spans both the hydrophobic β barrel of the OB-fold and the electrostatic, extended loop of the zinc finger. In addition to DNA binding motifs, the ID contains specific sites that contact Pol α, PCNA and MCM2-7 (see <PDOC00662>). Association with Pol α occurs via a hydrophobic patch termed the heat shock protein 10 (Hsp10)-like motif, whereas PCNA binds to a noncanonical PCNA interacting peptide (PIP) box, QxxM/I/LxxF/YF/Y [2,4].
The MCM10-CTD, although not present in unicellular eukaryotes and land plants, is conserved among metazoan species from nematodes to humans. Functionally, the CTD is similar to the ID, specifically in mediating interactions with DNA and Pol α. It contains a winged helix domain (WH) and two zinc chelating motifs, a CCCH zinc-finger (ZnF2) and a CCCC zinc-ribbon (ZnR) (see <PDB:2KWQ>). ZnF2 is required for the CTD to bind DNA, but the function of the ZnR has not been clearly defined, although it shares homology with the ZnRs found in archaeal and vertebrate MCM helicases [3,4].
The profiles we developed cover respectively the entire MCM-ID and MCM-CTD domains.
Last update:June 2025 / First entry.
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PROSITE methods (with tools and information) covered by this documentation:
| 1 | Authors | Robertson P.D. Warren E.M. Zhang H. Friedman D.B. Lary J.W. Cole J.L. Tutter A.V. Walter J.C. Fanning E. Eichman B.F. |
| Title | Domain architecture and biochemical characterization of vertebrate Mcm10. | |
| Source | J. Biol. Chem. 283:3338-3348(2008). | |
| PubMed ID | 18065420 | |
| DOI | 10.1074/jbc.M706267200 |
| 2 | Authors | Warren E.M. Vaithiyalingam S. Haworth J. Greer B. Bielinsky A.-K. Chazin W.J. Eichman B.F. |
| Title | Structural basis for DNA binding by replication initiator Mcm10. | |
| Source | Structure 16:1892-1901(2008). | |
| PubMed ID | 19081065 | |
| DOI | 10.1016/j.str.2008.10.005 |
| 3 | Authors | Robertson P.D. Chagot B. Chazin W.J. Eichman B.F. |
| Title | Solution NMR structure of the C-terminal DNA binding domain of Mcm10 reveals a conserved MCM motif. | |
| Source | J. Biol. Chem. 285:22942-22949(2010). | |
| PubMed ID | 20489205 | |
| DOI | 10.1074/jbc.M110.131276 |
| 4 | Authors | Baxley R.M. Bielinsky A.K. |
| Title | Mcm10: A Dynamic Scaffold at Eukaryotic Replication Forks. | |
| Source | Genes. (Basel). 8:0-0(2017). | |
| PubMed ID | 28218679 | |
| DOI | 10.3390/genes8020073 |
| 5 | Authors | Zhao X. Wang J. Jin D. Cheng J. Chen H. Li Z. Wang Y. Lou H. Zhu J.-K. Du X. Gong Z. |
| Title | AtMCM10 promotes DNA replication-coupled nucleosome assembly in Arabidopsis. | |
| Source | J. Integr. Plant. Biol. 65:203-222(2023). | |
| PubMed ID | 36541721 | |
| DOI | 10.1111/jipb.13438 |
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