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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*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. | *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: [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]. | ||
====Thioether Crosslinks==== | ====Thioether 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). | *Example: [[6e87]] (sulfur-carbon distance 1.83 Å). | ||
*Visualization: [https://firstglance.jmol.org/fg.htm?mol=6e87 View 6e87 in FirstGlance] | *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== | ||