Part of the cell · Metal-cluster and metalloenzyme maturation
Loading metals into enzymes
Not labelled on the cell picture.
Many enzymes only work with an iron, nickel or copper centre built into them. This machinery assembles and inserts those metal centres.
Proteins in the model: 90
Part of the model's 1051 proteins. Each group below is a book group, counted in the working count after the repeats and non-first-cell groups were removed. The proteins are not yet matched gene by gene.
| Group | Proteins |
|---|---|
| Magnesium Ions (Mg2+) - phosphate transfer | 1 |
| Magnesium Ions (Mg2+) - second system | 1 |
| Molybdenum Cofactor - oxidation-reduction | 1 |
| Molybdenum Cofactor - sulfur/nitrogen metabolism | 1 |
| Manganese Ions (Mn2+) - antioxidant defense | 2 |
| NAD+ transporter | 2 |
| Beta-alanine biosynthesis | 1 |
| Iron-sulfur cluster biosynthesis | 9 |
| [NiFe-4S] cluster synthesis | 6 |
| [5Fe-4S] cluster synthesis | 6 |
| [4Fe-4S] cluster synthesis | 6 |
| [Fe-Mo-Co] synthesis | 6 |
| [Fe-only] cluster synthesis | 6 |
| CODH/ACS complex metal clusters | 10 |
| Siderophore biosynthesis | 4 |
| Siderophore export | 1 |
| Ferrisiderophore transport | 4 |
| Sulfur mobilization | 2 |
| Sulfur transfer | 4 |
| Scaffold Proteins | 7 |
| Manganese utilization | 1 |
| Mo/W cofactor biosynthesis | 4 |
| Nickel center biosynthesis | 2 |
| Zinc utilization | 3 |
Its pathways
- NiFe-hydrogenase maturationatlas pathway5
- Metal installationatlas pathway3
- Not yet placed in a pathwayto sort7
If it fails
Enzymes are made correctly and stay useless, because the metal they need was never fitted. Both energy production and carbon fixation fail at once.
Enzymes go dead · 1–2 generations
What it depends on
- Mineral ions (not a separate group in the tree)Available iron, sulfur-related substrates, nickel, and other metals support the chosen cofactor assembly pathways.Book pp. 384–422, 499, 505
- Making the twenty amino acidsCysteine supplies sulfur to selected Fe–S cluster assembly systems.Book pp. 412–414, 500, 505
- Reading genes into RNA, Building proteins and folding themTranslation supplies scaffolds, sulfur-mobilization enzymes, and maturation factors.Book pp. 501–502, 505
What it supplies
- Building carbon into moleculesCODH/ACS and other selected carbon-metabolism enzymes require correctly assembled metal centers.Book pp. 384–407, 498
- Turning hydrogen into usable energySelected electron-transfer proteins require Fe–S clusters or other metal centers to function.Book pp. 384–407, 499
- Mineral ions (not a separate group in the tree)Metal binding and cofactor incorporation help allocate available metals into functional enzymes.Book pp. 384–422, 505
Dependencies are curated from the book at the level of the map’s systems and are not measured protein contacts. See all systems together.
How it is built and controlled
Counts from UniProt annotations of this group’s proteins.
Its place in the control layer
Assembly pathways
- Loading metals and clusters: , , , , , , , , , ,
From the control-layer pages. Which genes a regulator controls is mostly inferred from related bacteria, because Aquifex has no genetic system for testing it directly.
Origins
What needs to be explained
How were useful metal centres assembled, retained and coupled to catalysts under plausible environmental conditions?
What needs explaining. Explain metal-centre chemistry, controlled assembly and delivery to compatible protein recipients before the full modern maturation network existed.
Hurdles
- H-MET-1Available atomsThe problem. Iron–sulfur clusters need iron, sulfide and cysteine ligands together.Why it is hard. Free iron and sulfide precipitate as insoluble iron sulfide minerals rather than forming defined clusters.Chemistry before lifeStage 1: Ingredients made under plausible early-Earth conditionsShown: Iron, sulfide and simple ligands are expected in volcanic and hydrothermal settings.In the books: 9 open problems on metal cluster assembly ↗
- H-MET-2Productive assemblyThe problem. Cells build clusters on scaffold proteins, using a cysteine desulfurase to release sulfur and carrier proteins to deliver the finished cluster.Why it is hard. Without this machinery, iron and sulfur form many structures, most of them inactive.Molecular machinesStage 2: One step shown on its ownShown: Iron–sulfur clusters form on short peptides under laboratory conditions (Bonfio et al. 2017).In the books: 9 open problems on metal cluster assembly ↗
- H-MET-3StabilityThe problem. Clusters must stay intact while they work.Why it is hard. Iron–sulfur clusters are destroyed by oxygen and by heat unless the protein around them protects them.Molecular machinesStage 2: One step shown on its ownIn the books: 9 open problems on metal cluster assembly ↗
- H-MET-4Insertion into enzymesThe problem. Each cluster must be placed in a specific site of its target protein, with the right ligands, which tune its electrical properties.Why it is hard. A cluster outside its protein has the wrong properties; insertion is done by dedicated carrier proteins.Molecular machinesStage 1: Ingredients made under plausible early-Earth conditionsIn the books: 9 open problems on metal cluster assembly ↗
- H-MET-5Continuous rebuildingThe problem. Clusters must be repaired and rebuilt continuously, and the machinery that does it must be passed on to every daughter cell.Why it is hard. That machinery is made of proteins whose genes and synthesis themselves depend on iron–sulfur enzymes.Information and controlStage 0: Not yet addressed by experimentShown: not yet addressed by experiment.In the books: 9 open problems on metal cluster assembly ↗
Scope. Different metal centers are alternatives or specialized additions, not a single mandatory package. The origin of each assembly route requires a specified catalyst and environment.
Experimental progress. Structures of IscS complexes show different binding arrangements with sulfur-accepting partners, providing a molecular basis for directed sulfur transfer.
What would strengthen a natural account. Steps shown to work together under plausible early-Earth conditions, without a chemist choosing the reagents, purifying the products or changing conditions between steps, would strengthen a natural account of origins in proportion to what they explain. Loss of a claimed dependency or discovery of functional alternatives would weaken the corresponding design argument. Gaps in the record do not supply a numerical likelihood for either explanation.
Observations. Metalloenzymes may require separate machinery to build and insert active centres. Metal and sulfur handling must produce a compatible cofactor rather than an arbitrary aggregate.
Hallmarks that apply.
- H25 Cofactor dependency networks: Metalloenzymes may require separate machinery to build and insert active centres.
- H27 Material selection: Metal and sulfur handling must produce a compatible cofactor rather than an arbitrary aggregate.
- H28 Co-location of components: Scaffolds, carriers and recipient proteins must interact during delivery and maturation.
The author’s conclusion. The coordinated features give the author a positive reason to consider design within the wider cellular architecture. For this local system alone, they do not establish that design is uniquely the best historical explanation. The conservative inference is that the system contributes to a cumulative design case, with its weight conditional on the comparative evidence and on how much plausible natural pathways explain.
From the book article Metal Cluster Assembly, with its scientific references.
How it was discovered
- 1962Mortenson, Valentine and Carnahan isolate ferredoxin, an iron–sulfur protein, from Clostridium pasteurianum.Mortenson, Valentine & Carnahan, Biochemical and Biophysical Research Communications 7:448–452 (1962)
- 1988Günter Wächtershäuser proposes that life began on iron–sulfur minerals (the “iron–sulfur world”).Wächtershäuser, Systematic and Applied Microbiology 10:207–210 (1988)
- 1991The hyp genes needed to put the nickel–iron centre into hydrogenases are identified in E. coli.Lutz et al., Molecular Microbiology 5:123–135 (1991)
- 1993NifS is shown to be a cysteine desulfurase that supplies sulfur for iron–sulfur clusters.Zheng et al., PNAS 90:2754–2758 (1993)
- 1995The first crystal structure of a nickel–iron hydrogenase is solved.Volbeda et al., Nature 373:580–587 (1995)
- 1998The isc genes for general iron–sulfur cluster assembly, including the scaffold IscU, are described.Zheng et al., Journal of Biological Chemistry 273:13264–13272 (1998)
- 2017Ultraviolet light drives the formation of iron–sulfur clusters bound to short peptides under proposed prebiotic conditions.Bonfio et al., Nature Chemistry 9:1229–1234 (2017)
Each hurdle above is sorted by kind and by how far experiments have got (see “How hurdles are sorted” at the top).
All parts of the cell side by side: origins hub. The book articles:
- Metal Cluster Assembly: system page · full description · origins