Control layer
Assembly pathways
How proteins and complexes are folded, put in place, loaded and joined.
Folding helpers
Many proteins fold on their own, but helpers raise the yield and rescue proteins that misfold.
| Aquifex protein | Evidence (UniProt) | Home pathway |
|---|---|---|
| Trigger factor | Inferred from related proteins | Early folding support |
| Chaperone protein DnaK | Inferred from related proteins | Folding and stabilization |
| Chaperone protein DnaJ 1 | Inferred from related proteins | Not yet placed in a pathway |
| Protein GrpE | Inferred from related proteins | Early folding support |
| Chaperonin GroEL | Inferred from related proteins | Folding and stabilization |
| Co-chaperonin GroES | Inferred from related proteins | Folding and stabilization |
| Chaperone protein ClpB | Inferred from related proteins | Not yet placed in a pathway |
| Small heat shock protein (Class I) | Inferred from related proteins | Not yet placed in a pathway |
| 33 kDa chaperonin | Inferred from related proteins | Folding and stabilization |
Sending proteins to the membrane
Proteins destined for the membrane or beyond carry an address tag. The signal recognition particle and its receptor bring them to the Sec channel; YidC helps insert them; the Tat system moves proteins that are already folded; signal peptidases cut off the tag.
| Aquifex protein | Evidence (UniProt) | Home pathway |
|---|---|---|
| Signal recognition particle protein | Inferred from related proteins | Protein targeting |
| Signal recognition particle receptor FtsY | Inferred from related proteins | Protein targeting |
| Protein translocase subunit SecA | Inferred from related proteins | Protein translocation |
| Protein translocase subunit SecY | Seen as a protein | Protein translocation |
| Protein translocase subunit SecE | Seen as a protein | Not yet placed in a pathway |
| Protein-export membrane protein SecG | Seen as a protein | Protein translocation |
| Protein translocase subunit SecD | Inferred from related proteins | Protein translocation |
| Protein translocase subunit SecF | Inferred from related proteins | Protein translocation |
| Membrane protein insertase YidC | Inferred from related proteins | Protein export |
| Sec-independent protein translocase protein TatA 1 | Inferred from related proteins | Not yet placed in a pathway |
| Sec-independent protein translocase protein TatA 2 | Inferred from related proteins | Not yet placed in a pathway |
| Sec-independent protein translocase protein TatC | Seen as a protein | Protein translocation |
| Signal peptidase I | Inferred from related proteins | Protein export |
| Lipoprotein signal peptidase | Inferred from related proteins | Protein export |
Loading metals and clusters
Iron–sulfur clusters are built on a scaffold and handed to client proteins. The nickel–iron centre of hydrogenase needs its own set of helpers, and c-type cytochromes need their heme attached outside the cytoplasm.
| Aquifex protein | Evidence (UniProt) | Home pathway |
|---|---|---|
| Iron-sulfur cluster assembly scaffold protein IscU | Seen as a protein | Metal installation |
| cysteine desulfurase | Inferred from related proteins | Not yet placed in a pathway |
| Iron-sulfur cluster carrier protein | Inferred from related proteins | Not yet placed in a pathway |
| Hydrogenase maturation factor HypA | Inferred from related proteins | Not yet placed in a pathway |
| Hydrogenase expression/formation protein B | Inferred from related proteins | NiFe-hydrogenase maturation |
| Hydrogenase expression/formation protein HypD | Inferred from related proteins | NiFe-hydrogenase maturation |
| Hydrogenase expression/formation protein | Inferred from related proteins | NiFe-hydrogenase maturation |
| Carbamoyltransferase | Inferred from related proteins | NiFe-hydrogenase maturation |
| Cytochrome c-type biogenesis protein | Inferred from related proteins | Not yet placed in a pathway |
| Cytochrome c biogenesis protein | Predicted from the genome | Not yet placed in a pathway |
| Cytochrome c biogenesis protein | Predicted from the genome | Not yet placed in a pathway |
| ResB-like domain-containing protein | Predicted from the genome | Not yet placed in a pathway |
Building the ribosome
Ribosomes assemble from RNA and more than fifty proteins in order. These GTPases and maturation factors guide the late steps.
| Aquifex protein | Evidence (UniProt) | Home pathway |
|---|---|---|
| GTPase Era | Seen as a protein | Not yet placed in a pathway |
| GTPase Der | Inferred from related proteins | Not yet placed in a pathway |
| GTPase Obg | Inferred from related proteins | Not yet placed in a pathway |
| Ribosome maturation factor RimM | Inferred from related proteins | Recycling and rescue |
| Ribosome maturation factor RimP | Inferred from related proteins | Recycling and rescue |
The origins question
How can a cell build the machines that build its machines?
Many proteins fold without help, and short peptides can enter membranes on their own. The Sec channel and YidC belong to families found in all three domains of life.
Folding helpers, address-based delivery and metal loading all depend on proteins that are themselves made, folded and delivered by the same systems. The design analysis treats this as a case of the cell needing its own products to make itself.
Hallmarks that apply.
Sources
- Anfinsen, Science 181:223–230 (1973)
- Xu, Horwich & Sigler, Nature 388:741–750 (1997)
- Protein lists and evidence levels: UniProt proteome UP000000798