In some proteins (such as 4ZXB, 6CE9 which are respectively apo and halo forms of insulin receptors), I see ligands such as FUC (ALPHA-L-FUCOSE) and NAG(N-Acetylglucosamine). No matter which paper I checked I see no explanation for these ligands and therefore I assume they have to do with the experimental procedure but I do not quite understand what is their role. Do they stabilize a particular state of the protein? Note that the proteins above are determined by different methods the first one X-ray crystallography and the second by electron microscopy. I have no technical knowledge about the neither method so any input or link to a paper that actually explains them would be appreciated.



The insulin receptor is a glycoprotein. This is discussed, albeit briefly, in both papers for the structures you mentioned and the glycosylation is visible in the structures themselves. You can get more info in the following paper, among others:

Sparrow LG, Lawrence MC, Gorman JJ, Strike PM, Robinson CP, McKern NM, Ward CW. 2008. N-linked glycans of the human insulin receptor and their distribution over the crystal structure. Proteins 71(1):426-439.

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  • $\begingroup$ Yes this is the right answer. However I would make the following point (which you are welcome to incorporate). The PDB entry page visualizes manose, fucose and N-acetyl glucosamine as individual sugars. The paper you cite involves painstaking chemical analysis to show how the sugars are linked together into glycans (GlcNAc2Man6, GlcNAc4Man3Gal2Fuc etc.) and where they are linked to the protein. This emphases that the interpretation of X-ray crystal structures assumes linear polypeptide chains, but has no basis for assumptions on sugars, and the resolution is insufficient for this. $\endgroup$ – David May 23 '18 at 12:26
  • $\begingroup$ Thanks, since I was particularly interested in the insulin protein I will select this as the correct answer. As a side note to anyone who is interested this article discusses possible functional role of glycosylation for insulin: 1- sciencedirect.com/science/article/pii/S0167488900001099 2-jbc.org/content/274/32/22813.full $\endgroup$ – Sina May 23 '18 at 12:38


This addresses the general case, rather than the particular case of the insulin receptor, which is answered by @canadianer.

The General Problem of unexpected ligands in PDB structures

In preparing a relation database of about 400 protein structures I encountered the problem of distinguishing ligands that were substrates or cofactors of the enzyme from those that were not. And, believe me, the latter were widespread (and a real pain). In some cases it was obvious that the ‘ligand’ was the buffer (often MES) in which the protein was dissolved or ions such as sulphate. In the case of sugars, I assumed that the latter were present to aid crystalization. That view seems to be supported — in some cases at least — by a review by McPherson and Gavira. In a list of eight categories of additives that are used in protein crystallization they include:

(v) Osmolytes, co-solvents and cosmotropes are compounds that exert their effects at relatively high concentrations, 1 M or more, and include a wide range of molecules such as sucrose, trehalose and other sugars, proline, TMAO, glycine, betaine, taurine, sarcosine and a host of others. The effect of their inclusion in the mother liquor is to stabilize (or destabilize) the native conformation of the protein by altering the interaction of the surface of the protein with water, or by altering the hydration layer and possibly the structured waters.


As an example I cite the seven molecules of glycerol in 1B6G (shown below), a haloalkane dehalogenase from the bacterium, Xanthobacter autotrophicus. Although certain, usually pathogenic, bacteria do have glycosylation pathways, there is no suggestion that this is the case here, as indicated by the nature of the triose and the fact that the crystallization was performed in a glycerol solution:

Subsequently, the crystal was equilibrated for 0.5 h in a solution containing 70% ammonium sulfate and 100 mM MES buffer pH 5.0 and was then soaked for 3 h at room tempera- ture in 10 mM 1-chloropentane, 70% ammonium sulfate and 100 mM citrate buffer pH 5.0. A solution of 30%(w/v) PEG 6000, 20%(v/v) glycerol and 100 mM citrate pH 5.0 was applied as cryoprotectant during data collection.

haloalkane dehalogenase

Haloalkane dehalogenase, 1B6G. The glycerol molecules (grey and red) are shown in space-filling mode. (The yellow and red molecule is sulphate, the green one a chloride ion.)

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