Reactome | Proinsulin binds zinc and calcium forming Proinsulin:zinc:calcium

Proinsulin binds zinc and calcium forming Proinsulin:zinc:calcium

Stable Identifier

R-HSA-264976

Type

Reaction [binding]

Species

Homo sapiens

Compartment

Golgi lumen

ReviewStatus

5/5

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Proinsulin binds zinc and calcium forming Proinsulin:zinc:calcium

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In the presence of high concentrations of zinc and calcium, proinsulin spontaneously forms soluble complexes containing 6 molecules of proinsulin, 2 zinc ions, and 1 calcium ion. Zinc Transporters ZnT5, ZnT6, and ZnT7 are found in the membrane of the Golgi in pancreatic cells (and also in many other cell types). They play a role in maintaining the high zinc concentration in the Golgi lumen and thus catalyze the formation of the proinsulin-zinc-calcium complex. Other transporters, such as the newly identified ZnT9 and ZnT10, may also be involved but this is presently unknown.

Literature References

PubMed ID	Title	Journal	Year
9631292	The role of assembly in insulin's biosynthesis Steiner, D, Dodson, G	Curr Opin Struct Biol	1998
14704853	Overview of mammalian zinc transporters Nagao, M, Sasaki, R, Yamaguchi-Iwai, Y, Kambe, T	Cell Mol Life Sci	2004
2669954	Comparison of solution structural flexibility and zinc binding domains for insulin, proinsulin, and miniproinsulin Dunn, MF, Ko, HC, Kaarsholm, NC	Biochemistry	1989
16158220	Zinc-ligand interactions modulate assembly and stability of the insulin hexamer -- a review Dunn, MF	Biometals	2005
10521251	Role of metal ions in the T- to R-allosteric transition in the insulin hexamer Kadima, W	Biochemistry	1999