Protein crosslinks: Difference between revisions
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These crosslinks are formed either spontaneously during protein folding, or as a result of natural enzymatic processes. | These crosslinks are formed either spontaneously during protein folding, or as a result of natural enzymatic processes. | ||
<br>For '''interactive views with sources and further details''', click on the first link after each subtitle below. | <br>For '''interactive views with sources and further details''', click on the first link after each subtitle below. | ||
===Detection and Visualization=== | |||
[http://firstglance.jmol.org FirstGlance in Jmol] automatically detects and alerts you to the presence of any of the following seven types of covalent protein crosslinks. It provides "one click" tools to zoom in and examine any putative crosslink in detail, including display of the proximal [[electron density map]]. See the practical guide [[FirstGlance/Evaluating Protein Crosslinks]]. | |||
====Disulfide Crosslinks==== | ====Disulfide Crosslinks==== | ||
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*Example: Insulin [[9ins]] has 2 interchain and one intrachain disulfide bonds. Additional examples will be found in the lower left panel of FirstGlance when this example is viewed. | *Example: Insulin [[9ins]] has 2 interchain and one intrachain disulfide bonds. Additional examples will be found in the lower left panel of FirstGlance when this example is viewed. | ||
*Visualization: [https://firstglance.jmol.org/fg.htm?mol=9ins View 9ins in FirstGlance]. In [[FirstGlance]], in the Tools Tab, click Disulfides/S/Se. | *Visualization (right click link, open in a new browser tab): [https://firstglance.jmol.org/fg.htm?mol=9ins View 9ins in FirstGlance]. In [[FirstGlance]], in the Tools Tab, click Disulfides/S/Se. | ||
====Isopeptide Crosslinks==== | ====Isopeptide Crosslinks==== | ||
[[Isopeptide bonds]] | See [[Isopeptide bonds]] for a detailed description and examples. An estimate of the frequency of isopeptide crosslinks in the PDB may not be available. | ||
*A text search for "isopeptide" at RCSB.Org gives ~400 hits (July, 2021). | *A text search for "isopeptide" at RCSB.Org gives ~400 hits (July, 2021). | ||
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*Example: Bacterial pilus adhesin [[2xi9]] has 2 isopeptide bonds (and 2 thioester bonds). Additional examples will be found in the lower left panel of FirstGlance when this example is viewed. | *Example: Bacterial pilus adhesin [[2xi9]] has 2 isopeptide bonds (and 2 thioester bonds). Additional examples will be found in the lower left panel of FirstGlance when this example is viewed. | ||
*Visualization: [https://firstglance.jmol.org/fg.htm?mol=2xi9 View 2xi9 in FirstGlance] | *Visualization (right click link, open in a new browser tab): [https://firstglance.jmol.org/fg.htm?mol=2xi9 View 2xi9 in FirstGlance]. | ||
====Thioester Crosslinks==== | ====Thioester Crosslinks==== | ||
[[Thioester protein crosslinks | See [[Thioester protein crosslinks]] for a detailed description and examples. An estimate of the frequency of thioester crosslinks in the PDB may not be available. | ||
*A text search for "thioester" at RCSB.Org gives ~2,000 hits (out of ~180,000 total, July, 2021). | *A text search for "thioester" at RCSB.Org gives ~2,000 hits (out of ~180,000 total, July, 2021). | ||
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*Adding "and not thioesterase" to the PDBe search reduced the hits to ~500. >30 hits were tested but only a couple had thioester bonds. | *Adding "and not thioesterase" to the PDBe search reduced the hits to ~500. >30 hits were tested but only a couple had thioester bonds. | ||
*Example: Bacterial pilus adhesin [[2xi9]] has 2 thioester bonds (and 2 isopeptide bonds). Additional examples will be found in the lower left panel of FirstGlance when this example is viewed. | *Example: Bacterial pilus adhesin [[2xi9]] has 2 thioester bonds (and 2 isopeptide bonds). Additional examples will be found at [[Thioester protein crosslinks]], and in the lower left panel of FirstGlance when this example is viewed. | ||
*Visualization (right click link, open in a new browser tab): [https://firstglance.jmol.org/fg.htm?mol=2xi9 View 2xi9 in FirstGlance]. | |||
====Thioether Crosslinks==== | |||
*Visualization: [https://firstglance.jmol.org/fg.htm?mol= | See [[Thioether protein crosslinks]] for a detailed description and examples. These include Cys-Tyr crosslinks. Cys-ligand thioether links are common but do not necessarily crosslink polypeptides. An estimate of the frequency of thioether crosslinks in the PDB may not be available. | ||
*Example: [[6e87]] (sulfur-carbon distance 1.83 Å). | |||
*Visualization (right click link, open in a new browser tab): [https://firstglance.jmol.org/fg.htm?mol=6e87 View 6e87 in FirstGlance]. | |||
====Ester Crosslinks==== | ====Ester Crosslinks==== | ||
See [[Ester protein crosslinks]] for a detailed description and examples. An estimate of the frequency of ester crosslinks in the PDB may not be available. Thr-Gln ester crosslinks were first reported in 2013<ref name="kwon2013">PMID:24344302</ref>. | |||
*Example: Bacterial pilus repeat domains [[4mkm]] has 2 interchain Thr-Gln ester bonds. Additional examples will be found in the lower left panel of FirstGlance when this example is viewed. | *Example: Bacterial pilus repeat domains [[4mkm]] has 2 interchain Thr-Gln ester bonds. Additional examples will be found in the lower left panel of FirstGlance when this example is viewed. | ||
*Visualization: [https://firstglance.jmol.org/fg.htm?mol=4mkm View 4mkm in FirstGlance]. | *Visualization (right click link, open in a new browser tab): [https://firstglance.jmol.org/fg.htm?mol=4mkm View 4mkm in FirstGlance]. | ||
====Histidine-tyrosine protein crosslinks==== | |||
See [[Histidine-tyrosine protein crosslinks]] for a detailed description and examples. An estimate of the frequency of ester crosslinks in the PDB may not be available. | |||
====Lysine-Cysteine NOS Crosslinks==== | ====Lysine-Cysteine NOS Crosslinks==== | ||
See [[Lysine-cysteine NOS bonds]] for a detailed description and examples. NOS bonds are redox switches in many enzymes. These were most convincingly documented in 2021 by Wensien ''et al.''<ref name="wensien2021">PMID: 33953398</ref>. They reported that following a search of the entire PDB, they "identified a number of proteins from all domains of life that are highly likely to possess one or more NOS bridges". However, because the existence of NOS bonds has not been widely recognized, they were not modeled in many proteins structures in which they actually occur. | |||
*Example: [[6zx4]] was analyzed in depth and provided the first documented case. Additional examples will be found in the lower left panel of FirstGlance when this example is viewed. | *Example: [[6zx4]] was analyzed in depth and provided the first documented case. Additional examples will be found in the lower left panel of FirstGlance when this example is viewed. | ||
*Visualization: [https://firstglance.jmol.org/fg.htm?mol=6zx4 View 6zx4 in FirstGlance] | *Visualization (right click link, open in a new browser tab): [https://firstglance.jmol.org/fg.htm?mol=6zx4 View 6zx4 in FirstGlance]. | ||
==Artificial Crosslinks== | ==Artificial Crosslinks== | ||
[To be written] | [To be written - feel free to contribute] | ||
==Notes & References== | ==Notes & References== | ||
<references /> | <references /> | ||
Latest revision as of 03:25, 24 January 2022
Proteins are linear (unbranched) polypeptide chains of amino acids. The subject of this article is covalent crosslinks between polypeptides, either between protein chains (interchain crosslinks), or within chains (intrachain crosslinks).
Natural CrosslinksNatural Crosslinks
These crosslinks are formed either spontaneously during protein folding, or as a result of natural enzymatic processes.
For interactive views with sources and further details, click on the first link after each subtitle below.
Detection and VisualizationDetection and Visualization
FirstGlance in Jmol automatically detects and alerts you to the presence of any of the following seven types of covalent protein crosslinks. It provides "one click" tools to zoom in and examine any putative crosslink in detail, including display of the proximal electron density map. See the practical guide FirstGlance/Evaluating Protein Crosslinks.
Disulfide CrosslinksDisulfide Crosslinks
Disulfide bonds are the most common protein crosslinks. About 23% of protein structures in the PDB have disulfide bonds (July, 2021[1]).
- Example: Insulin 9ins has 2 interchain and one intrachain disulfide bonds. Additional examples will be found in the lower left panel of FirstGlance when this example is viewed.
- Visualization (right click link, open in a new browser tab): View 9ins in FirstGlance. In FirstGlance, in the Tools Tab, click Disulfides/S/Se.
Isopeptide CrosslinksIsopeptide Crosslinks
See Isopeptide bonds for a detailed description and examples. An estimate of the frequency of isopeptide crosslinks in the PDB may not be available.
- A text search for "isopeptide" at RCSB.Org gives ~400 hits (July, 2021).
- A text search at PDBe gives ~12,000 hits (July, 2021). In a small sample of the latter hits, none contained the term "isopeptide". Also based on a small sample, some entries that contain verified isopeptide bonds do not contain the term (for example, 5jqf).
- Example: Bacterial pilus adhesin 2xi9 has 2 isopeptide bonds (and 2 thioester bonds). Additional examples will be found in the lower left panel of FirstGlance when this example is viewed.
- Visualization (right click link, open in a new browser tab): View 2xi9 in FirstGlance.
Thioester CrosslinksThioester Crosslinks
See Thioester protein crosslinks for a detailed description and examples. An estimate of the frequency of thioester crosslinks in the PDB may not be available.
- A text search for "thioester" at RCSB.Org gives ~2,000 hits (out of ~180,000 total, July, 2021).
- A text search at PDBe gives ~1,400 hits (July, 2021). Among a sample of 5 of the PDBe hits (the first of every 100 in a listing sorted with best resolution at the top), none had thioester bonds, but most contained terms such as "thioesterase" or "thioester".
- Adding "and not thioesterase" to the PDBe search reduced the hits to ~500. >30 hits were tested but only a couple had thioester bonds.
- Example: Bacterial pilus adhesin 2xi9 has 2 thioester bonds (and 2 isopeptide bonds). Additional examples will be found at Thioester protein crosslinks, and in the lower left panel of FirstGlance when this example is viewed.
- Visualization (right click link, open in a new browser tab): View 2xi9 in FirstGlance.
Thioether CrosslinksThioether Crosslinks
See Thioether protein crosslinks for a detailed description and examples. These include Cys-Tyr crosslinks. Cys-ligand thioether links are common but do not necessarily crosslink polypeptides. An estimate of the frequency of thioether crosslinks in the PDB may not be available.
- Example: 6e87 (sulfur-carbon distance 1.83 Å).
- Visualization (right click link, open in a new browser tab): View 6e87 in FirstGlance.
Ester CrosslinksEster Crosslinks
See Ester protein crosslinks for a detailed description and examples. An estimate of the frequency of ester crosslinks in the PDB may not be available. Thr-Gln ester crosslinks were first reported in 2013[2].
- Example: Bacterial pilus repeat domains 4mkm has 2 interchain Thr-Gln ester bonds. Additional examples will be found in the lower left panel of FirstGlance when this example is viewed.
- Visualization (right click link, open in a new browser tab): View 4mkm in FirstGlance.
Histidine-tyrosine protein crosslinksHistidine-tyrosine protein crosslinks
See Histidine-tyrosine protein crosslinks for a detailed description and examples. An estimate of the frequency of ester crosslinks in the PDB may not be available.
Lysine-Cysteine NOS CrosslinksLysine-Cysteine NOS Crosslinks
See Lysine-cysteine NOS bonds for a detailed description and examples. NOS bonds are redox switches in many enzymes. These were most convincingly documented in 2021 by Wensien et al.[3]. They reported that following a search of the entire PDB, they "identified a number of proteins from all domains of life that are highly likely to possess one or more NOS bridges". However, because the existence of NOS bonds has not been widely recognized, they were not modeled in many proteins structures in which they actually occur.
- Example: 6zx4 was analyzed in depth and provided the first documented case. Additional examples will be found in the lower left panel of FirstGlance when this example is viewed.
- Visualization (right click link, open in a new browser tab): View 6zx4 in FirstGlance.
Artificial CrosslinksArtificial Crosslinks
[To be written - feel free to contribute]
Notes & ReferencesNotes & References
- ↑ In July, 2021, the PDB had ~180,000 entries. Advanced search at RCSB.Org for "Polymer molecuar features: polymer entity type = protein" and "Deposited entry features: Disulfide bond count per deposited model > 0" gave ~41,000 hits, or about 23%.
- ↑ Kwon H, Squire CJ, Young PG, Baker EN. Autocatalytically generated Thr-Gln ester bond cross-links stabilize the repetitive Ig-domain shaft of a bacterial cell surface adhesin. Proc Natl Acad Sci U S A. 2013 Dec 16. PMID:24344302 doi:http://dx.doi.org/10.1073/pnas.1316855111
- ↑ Wensien M, von Pappenheim FR, Funk LM, Kloskowski P, Curth U, Diederichsen U, Uranga J, Ye J, Fang P, Pan KT, Urlaub H, Mata RA, Sautner V, Tittmann K. A lysine-cysteine redox switch with an NOS bridge regulates enzyme function. Nature. 2021 May 5. pii: 10.1038/s41586-021-03513-3. doi:, 10.1038/s41586-021-03513-3. PMID:33953398 doi:http://dx.doi.org/10.1038/s41586-021-03513-3