MinC is the septum site-determining protein that functions as the primary effector of the Min system in Bacillus subtilis. It acts as a direct inhibitor of FtsZ polymerization, preventing Z-ring formation at cell poles to ensure accurate midcell division. MinC has a bipartite domain architecture: the N-terminal domain (MinCN) binds to the H9/H10 helix region of FtsZ and inhibits FtsZ filament bundling/stability, while the C-terminal domain (MinCC) mediates dimerization, MinD binding, and targeting to FtsZ via the C-terminal peptide (CTP). Unlike E. coli, B. subtilis lacks MinE and instead uses the DivIVA-MinJ-MinCD system for spatial regulation. DivIVA senses negative membrane curvature at cell poles, recruits MinJ (an integral membrane protein), which in turn bridges to MinCD. This creates a stationary bipolar gradient that concentrates MinC at cell poles, preventing aberrant polar septation while allowing midcell Z-ring assembly. During cytokinesis, DivIVA/MinJ form double rings flanking the nascent septum, spatially separating MinC from the active division site. Loss of minC leads to characteristic minicell formation (small DNA-less polar divisions), cell elongation, and persistent polar FtsZ rings. MinC also contributes to disassembly of completed cytokinetic rings after division. The MinCD complex promotes FtsZ filament fragmentation at membranes through a mechanism distinct from simple sequestration.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000918 division septum site selection | IBA GO_REF:0000033 | ACCEPT | Summary: MinC is a central player in division septum site selection in B. subtilis. It functions within the DivIVA-MinJ-MinCD system to spatially regulate where the Z-ring can form, preventing polar septation and ensuring midcell division (PMID:23577149). Reason: This is a core function of MinC. The Min system represents a site-specific inhibitor of FtsZ polymerization that prevents re-initiation of division at improper sites (PMID:23577149). Loss of Min function leads to polar divisions generating minicells. The IBA annotation is phylogenetically sound and represents the primary biological process role of MinC. Supporting Evidence: PMID:23577149 The Min system represents a site-specific inhibitor of FtsZ polymerization that prevents re-initiation of division immediately after a round of division has finished [10], [11]. In the absence of a functional Min system bacteria will frequently divide close to one of the cell poles and generate the so-called minicells, small DNA-less cells that are incapable of further reproduction [12], [13]. file:BACSU/minC/minC-deep-research-falcon.md See deep research file for comprehensive analysis |
| GO:0004857 enzyme inhibitor activity | IBA GO_REF:0000033 | MODIFY | Summary: MinC directly inhibits FtsZ polymerization through protein-protein interaction rather than classical enzyme inhibition. While FtsZ has GTPase activity, MinC does not inhibit the GTPase activity but rather prevents higher-order polymer assembly (PMID:23577149). Reason: While this annotation captures that MinC has inhibitory activity, the term "enzyme inhibitor activity" (GO:0004857) is misleading. MinC inhibits FtsZ polymer assembly, not FtsZ enzymatic (GTPase) activity. The literature explicitly states that MinC did not inhibit FtsZ GTPase activity (PMID:23577149). MinC binds to FtsZ (a tubulin homolog) and prevents higher-order structure assembly. A more accurate term would be tubulin binding (GO:0015631) since FtsZ is the bacterial tubulin homolog, or the BP term negative regulation of protein polymerization (GO:0032272). Proposed replacements: tubulin binding Supporting Evidence: PMID:23577149 Initial biochemical experiments revealed that MinC (in the form of a MalE-MinC fusion) inhibited the sedimentation of FtsZ polymers but did not inhibit FtsΕΉs GTPase activity [16]. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: MinC is a cytoplasmic protein that is recruited to the membrane via its interaction with MinD. It does not have intrinsic membrane-binding capability but is functionally targeted to membrane-proximal locations through the MinCD complex (PMID:23577149). Reason: MinC is described as "a cytoplasmic protein that has the ability to inhibit FtsZ polymerization" (PMID:23577149). While it is recruited to the membrane through MinD interaction, its baseline localization without MinD would be cytosolic. The IBA annotation is appropriate for the intrinsic localization of the protein. Supporting Evidence: PMID:23577149 MinC is a cytoplasmic protein that has the ability to inhibit FtsZ polymerization in vitro and, thus, represents the ultimate effector of Min function [16], [17]. |
| GO:0007105 cytokinesis, division site positioning | IBA GO_REF:0000033 | ACCEPT | Summary: MinC directly participates in positioning the division site by preventing FtsZ ring assembly at inappropriate locations (cell poles), thereby ensuring midcell positioning of the cytokinetic apparatus (PMID:23577149). Reason: This is essentially the same core function as GO:0000918 (division septum site selection) - both describe MinC's role in spatial control of cell division. The annotation accurately reflects MinC's function in ensuring the Z-ring forms at midcell rather than at poles. Both terms are acceptable as they capture the same fundamental biological role from slightly different perspectives. Supporting Evidence: PMID:23577149 MinC, an inhibitor of FtsZ polymerization that plays a crucial role in the spatial control of Z ring formation. |
| GO:0060187 cell pole | IBA GO_REF:0000033 | ACCEPT | Summary: MinC is enriched at cell poles in B. subtilis through the DivIVA-MinJ-MinD targeting system. DivIVA senses negative membrane curvature at poles, recruits MinJ, which bridges to MinCD. This polar localization is essential for preventing polar Z-ring formation (PMID:23577149). Reason: MinC localization to cell poles is a core aspect of its function in B. subtilis. The DivIVA-MinJ-MinCD system creates a stationary bipolar gradient that concentrates Min activity at cell poles. This is well-established in the literature and the IBA annotation is phylogenetically appropriate. Supporting Evidence: PMID:23577149 In B. subtilis, localization of MinCD requires DivIVA, a pole-marking protein conserved in Gram-positive bacteria [22]β[26]. |
| GO:0000902 cell morphogenesis | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: This IEA annotation is derived from InterPro domain mapping. While MinC mutants do show morphological phenotypes (elongated cells, minicells), this is an indirect consequence of division site misregulation rather than a direct role in cell morphogenesis. Reason: The term cell morphogenesis is broader than MinC's actual function. MinC's primary role is in division site selection/FtsZ inhibition. The morphological phenotypes observed in minC mutants (elongation, minicells) are secondary consequences of aberrant division. This annotation is not wrong but represents a non-core, indirect effect. The IEA source (InterPro) likely infers this from the MinC domain family rather than specific experimental evidence for morphogenesis function. Supporting Evidence: PMID:23577149 In the absence of a functional Min system bacteria will frequently divide close to one of the cell poles and generate the so-called minicells, small DNA-less cells that are incapable of further reproduction [12], [13]. |
| GO:0000917 division septum assembly | IEA GO_REF:0000043 | MODIFY | Summary: This IEA annotation from UniProtKB keyword mapping indicates involvement in septum assembly. MinC actually negatively regulates septum assembly at inappropriate sites rather than promoting it. It may also contribute to disassembly of the divisome after cytokinesis. Reason: MinC is an inhibitor of Z-ring/septum formation, not a promoter. The term "division septum assembly" (GO:0000917) implies positive involvement in building the septum, but MinC prevents septum formation at poles. A more accurate annotation would be "negative regulation of division septum assembly" or "regulation of cell septum assembly" to capture its inhibitory role. The Min system also promotes disassembly of completed cytokinetic rings. Proposed replacements: regulation of cell septum assembly Supporting Evidence: PMID:23577149 The Min system represents a site-specific inhibitor of FtsZ polymerization that prevents re-initiation of division immediately after a round of division has finished [10], [11]. |
| GO:0051301 cell division | IEA GO_REF:0000043 | ACCEPT | Summary: MinC is clearly involved in cell division as part of the Min system that ensures proper spatial control of the divisome. This broad term captures MinC's role in the cell division process. Reason: This is a general but accurate annotation. MinC is unambiguously involved in regulating cell division, specifically the spatial aspect. While more specific terms like GO:0000918 (division septum site selection) better capture its precise function, this broader annotation is not incorrect. The IEA derivation from UniProt keywords is appropriate. Supporting Evidence: PMID:23577149 Cell division in bacteria is regulated by proteins that interact with FtsZ and modulate its ability to polymerize into the Z ring structure. |
| GO:0051726 regulation of cell cycle | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: This broad IEA annotation from combined automated methods indicates involvement in cell cycle regulation. MinC affects the cell division step of the cell cycle through spatial control of Z-ring formation. Reason: While technically accurate (MinC does regulate an aspect of the cell cycle), this term is very broad and does not capture the specific function of MinC. More precise annotations exist (division septum site selection, cytokinesis division site positioning). This can be kept as a non-core annotation that captures the general cellular context without implying MinC is a primary cell cycle regulator in the classic sense (DNA replication, checkpoints, etc.). Supporting Evidence: PMID:23577149 The remarkable spatiotemporal fidelity of bacterial division, which is always symmetrical and in sync with DNA replication, can be explained by the joint action of the Min system and that of the nucleoid occlusion proteins, such as Noc in B. subtilis and SlmA in E. coli, which prevent FtsZ assembly over unreplicated nucleoids [14], [15]. |
| GO:0090529 cell septum assembly | IEA GO_REF:0000104 | MODIFY | Summary: Similar to GO:0000917, this annotation implies involvement in septum assembly. MinC negatively regulates septum assembly at poles rather than directly participating in building septa. Reason: As with GO:0000917, this term suggests positive involvement in septum construction. MinC inhibits Z-ring/septum formation at inappropriate sites. A regulatory term would be more accurate. This IEA annotation from sequence feature transfer does not capture the inhibitory nature of MinC's function. Proposed replacements: regulation of cell septum assembly Supporting Evidence: PMID:23577149 This indicated that MinC does not inhibit the head-to- tail polymerization of FtsZ subunits into its basic (proto)filaments, but, instead, prevents the assembly of FtsZ into higher order structures, such as bundles of filaments. |
| GO:1901891 regulation of cell septum assembly | IEA GO_REF:0000002 | ACCEPT | Summary: This InterPro-derived annotation accurately captures MinC's regulatory role in septum assembly. MinC negatively regulates septum formation at cell poles while indirectly enabling proper midcell septation. Reason: This is an appropriate annotation for MinC. The term "regulation of cell septum assembly" correctly indicates that MinC modulates where and when septa form without implying direct positive involvement in septum construction. MinC prevents septum formation at poles through FtsZ inhibition, which is regulatory. Supporting Evidence: PMID:23577149 The Min system represents a site-specific inhibitor of FtsZ polymerization that prevents re-initiation of division immediately after a round of division has finished [10], [11]. |
| GO:0005515 protein binding | IPI PMID:25374563 Protein-tyrosine phosphorylation interaction network in Baci... | MODIFY | Summary: This annotation is based on detection of the MinD-MinC complex in far Western blotting experiments (PMID:25374563). While the interaction is real, the term "protein binding" is too vague and uninformative. Reason: The term GO:0005515 (protein binding) is discouraged for annotation as it provides no information about the specific function. MinC has well-characterized binding partners: FtsZ (its target for inhibition) and MinD (its membrane recruiter). More informative molecular function terms should be used. A more specific term like tubulin binding (GO:0015631) would be appropriate since FtsZ is the bacterial tubulin homolog. Proposed replacements: tubulin binding Supporting Evidence: PMID:25374563 In this assay we detected the expected MinD-MinC complex and confirmed the physical interaction between MinD and PtkA, but not TkmA, in agreement with the two-hybrid. PMID:23577149 Biochemical characterization of some of the mutant proteins showed that they exhibited normal polymerization properties but reduced interaction with MinC, as expected for binding site mutations. |
| GO:0032272 negative regulation of protein polymerization | IDA PMID:23577149 Genetic and biochemical characterization of the MinC-FtsZ in... | ACCEPT | Summary: This IDA annotation is directly supported by experimental evidence showing MinC inhibits FtsZ polymer assembly in vitro. Light scattering, electron microscopy, and biochemical assays demonstrate MinC prevents FtsZ higher-order structure formation (PMID:23577149). Reason: This is a core biological process annotation with direct experimental support. The study by Blasios et al. 2013 demonstrates that B. subtilis MinC inhibits FtsZ polymerization biochemically. EM shows shorter, less bundled filaments; light scattering confirms reduced polymer mass. The mechanism involves MinCN binding near H9/H10 helices affecting polymer stability and MinCC binding the FtsZ C-terminal peptide for targeting. Supporting Evidence: PMID:23577149 Indeed, EM and rheology measurements showed that FtsZ polymers formed in the presence of MinC are less bundled, and have fewer lateral contacts and interconnections [33]. |
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Download this section (compressed HTML)Q: What are the specific residues in B. subtilis MinC that mediate FtsZ binding versus MinD binding? While the MinC-FtsZ interaction has been mapped on the FtsZ side, the specific MinC residues involved are less well characterized in B. subtilis compared to E. coli.
Q: Does MinC play a role in asymmetric division during sporulation, and if so, how is its activity modulated? The UniProt entry mentions MinCD role in sporulation septum formation, but the specific regulatory mechanisms are not fully elucidated.
Experiment: Structure determination of B. subtilis MinC-FtsZ complex to understand species-specific differences in inhibition mechanism. PMID:23577149 notes that while MinC-FtsZ interaction architecture is conserved, the specific binding surface differs between E. coli and B. subtilis, suggesting mechanistic differences that could be resolved structurally.
Hypothesis: The B. subtilis MinC-FtsZ interaction surface differs from E. coli due to species-specific adaptations in the H9/H10 helix region.
Experiment: Super-resolution imaging of MinC dynamics during sporulation versus vegetative growth to understand how the Min system is remodeled during asymmetric sporulation division. This could reveal regulatory mechanisms that modulate MinC activity during developmental transitions.
Hypothesis: MinC localization and activity are dynamically regulated during sporulation to permit asymmetric division while preventing polar minicell formation.
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