5JYQ

Structure of Conus Geographus insulin G1

Summary for 5JYQ

• Entry DOI: 10.2210/pdb5jyq/pdb
• Descriptor: Insulin 1, Insulin 1b, SULFATE ION, ... (4 entities in total)
• Functional Keywords: venom insulin, hormone
• Biological source: Conus geographus (Geography cone); More
• Total number of polymer chains: 2
• Total formula weight: 5256.87

Authors

Lawrence, M.C.,Menting, J.,Norton, R.S.,Safavi-Hemami, H. (deposition date: 2016-05-15, release date: 2016-09-07, Last modification date: 2023-11-15)

Primary citation

Menting, J.G.,Gajewiak, J.,MacRaild, C.A.,Chou, D.H.,Disotuar, M.M.,Smith, N.A.,Miller, C.,Erchegyi, J.,Rivier, J.E.,Olivera, B.M.,Forbes, B.E.,Smith, B.J.,Norton, R.S.,Safavi-Hemami, H.,Lawrence, M.C.
A minimized human insulin-receptor-binding motif revealed in a Conus geographus venom insulin.
Nat.Struct.Mol.Biol., 23:916-920, 2016

PubMed Abstract: Insulins in the venom of certain fish-hunting cone snails facilitate prey capture by rapidly inducing hypoglycemic shock. One such insulin, Conus geographus G1 (Con-Ins G1), is the smallest known insulin found in nature and lacks the C-terminal segment of the B chain that, in human insulin, mediates engagement of the insulin receptor and assembly of the hormone's hexameric storage form. Removal of this segment (residues B23-B30) in human insulin results in substantial loss of receptor affinity. Here, we found that Con-Ins G1 is monomeric, strongly binds the human insulin receptor and activates receptor signaling. Con-Ins G1 thus is a naturally occurring B-chain-minimized mimetic of human insulin. Our crystal structure of Con-Ins G1 reveals a tertiary structure highly similar to that of human insulin and indicates how Con-Ins G1's lack of an equivalent to the key receptor-engaging residue Phe is mitigated. These findings may facilitate efforts to design ultrarapid-acting therapeutic insulins.

PubMed: 27617429
DOI: 10.1038/nsmb.3292

Experimental method

X-RAY DIFFRACTION (1.95 Å)