PDBsum entry: 2kqp

Hormone

PDB id: 2kqp

Contents

Protein chain

86 a.a. *

* Residue conservation analysis

PDB id:

2kqp

Name:

Hormone

Title:

Nmr structure of proinsulin

Structure:

Insulin. Chain: a. Synonym: insulin b chain, insulin a chain. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ins. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

Y.Yang,Q.X.Hua,R.B.Mackin,M.A.Weiss

Key ref:

Y.Yang et al. (2010). Solution structure of proinsulin. Connecting-domain flexibility and prohormone processing. J Biol Chem, 285, 7847-7851. PubMed id: 20106974 DOI: 10.1074/jbc.C109.084921

Date:

12-Nov-09 Release date: 26-Jan-10

Protein chain

P01308  (INS_HUMAN) -  Insulin

Seq: 110 a.a.

Struc: 86 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (2 terms)
• Biological process: carbohydrate metabolic process (52 terms)
• Biochemical function: protein binding (4 terms)

DOI no: 10.1074/jbc.C109.084921

J Biol Chem 285:7847-7851 (2010)

PubMed id: 20106974

Solution structure of proinsulin. Connecting-domain flexibility and prohormone processing.

Y.Yang, Q.X.Hua, J.Liu, E.H.Shimizu, M.H.Choquette, R.B.Mackin, M.A.Weiss.

ABSTRACT

The folding of proinsulin, the single-chain precursor of insulin in pancreatic beta-cells, ensures native disulfide pairing in the endoplasmic reticulum. Mutations that impairing its folding cause permanent neonatal-onset diabetes mellitus. Whereas the classical structure of insulin is well characterized, proinsulin is refractory to crystallization. Here, we employ heteronuclear NMR spectroscopy to determine the solution structure of a monomeric analogue (DKP-proinsulin). The structure contains a native-like insulin moiety (A- and B domains) in the T conformation. The connecting polypeptide (C domain) is largely but not completely disordered. Although the BC junction is flexible, residues near the CA junction exhibit partial alpha-helical-like chemical shifts similar to those of the contiguous A-domain alpha-helix (residues A1-A8). These shifts are attenuated relative to canonical alpha-helices, however, suggesting a molten segmental conformation. The A1-A8 segment is likewise molten in the corresponding insulin monomer. We propose that flexibility at the BC and CA junctions facilitates disulfide pairing and prohormone processing in the beta-cell. The structure of proinsulin as an engineered monomer provides a foundation for comparative studies of diabetes-associated variants.