Protein crosslinks

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.

Disulfide BondsDisulfide Bonds

Disulfide bonds are the most common protein crosslinks. About 23% of protein structures in the PDB have disulfide bonds (July, 2021).

• Example: Insulin 9ins has 2 interchain and one intrachain disulfide bonds.

• Visualization: View 9ins in FirstGlance. In FirstGlance, in the Tools Tab, click Disulfides/S/Se.

Isopeptide BondsIsopeptide Bonds

Isopeptide bonds are less common, but an estimate of their frequency may not be available. A text search for "isopeptide" at RCSB.Org gives ~400 hits, while 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.

• Example: Bacterial pilus adhesin 2xi9 has 2 isopeptide bonds (and 2 thioester bonds).

• Visualization: View 2xi9 in FirstGlance. If you see "➤➤Show more details" in the Molecule Information Tab, click on that.

Thioester BondsThioester Bonds

Thioester bonds: Again, an estimate of frequency may not be available. A text search for "thioester" at RCSB.Org gives ~2,000 hits, while a text search at PDBe gives ~1,400 hits (July, 2021). Among a sample of 5 of the PDBe hits (every 100th in the listing), none had thioester bonds, but most contained terms such as "thioesterase" or "thioester". Adding "and not thioesterase" reduced the hits to ~500. RCSB Advanced Search has "Biologically Interesting Molecules (BIRD): BIRD Type = Thioester", which gives 19 hits (July, 2021). However, only 2% of entries have BIRD annotations.

• • Example: Bacterial pilus adhesin 2xi9 has 2 thioester bonds (and 2 isopeptide bonds).

• • Visualization: View 2xi9 in FirstGlance. If you see "➤➤Show more details" in the Molecule Information Tab, click on that.