4UNH: Human Insulin B26gly Mutant Crystal Structure

The structural characterization of the insulin-insulin receptor (IR) interaction still lacks the conformation of the crucial B21-B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that in all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms.
PDB ID: 4UNHDownload
MMDB ID: 123912
PDB Deposition Date: 2014/5/28
Updated in MMDB: 2014/10
Experimental Method:
x-ray diffraction
Resolution: 2.75  Å
Source Organism:
Similar Structures:
Biological Unit for 4UNH: dimeric; determined by software (PISA)
Molecular Components in 4UNH
Label Count Molecule
Proteins (2 molecules)
Insulin a Chain(Gene symbol: INS)
Molecule annotation
Insulin B Chain(Gene symbol: INS)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB