2KQP

NMR Structure of Proinsulin


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 90 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with acceptable covalent geometry 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Solution structure of proinsulin: connecting domain flexibility and prohormone processing.

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

(2010) J Biol Chem 285: 7847-7851

  • DOI: https://doi.org/10.1074/jbc.C109.084921
  • Primary Citation of Related Structures:  
    2KQP

  • PubMed Abstract: 

    The folding of proinsulin, the single-chain precursor of insulin, ensures native disulfide pairing in pancreatic beta-cells. Mutations that impair folding cause neonatal diabetes mellitus. Although the classical structure of insulin is well established, proinsulin is refractory to crystallization. Here, we employ heteronuclear NMR spectroscopy to characterize a monomeric analogue. Proinsulin contains a native-like insulin moiety (A- and B-domains); the tethered connecting (C) domain (as probed by {(1)H}-(15)N nuclear Overhauser enhancements) is progressively less ordered. Although the BC junction is flexible, residues near the CA junction exhibit alpha-helical-like features. Relative to canonical alpha-helices, however, segmental (13)C(alpha/beta) chemical shifts are attenuated, suggesting that this junction and contiguous A-chain residues are molten. We propose that flexibility at each C-domain junction facilitates prohormone processing. Studies of protease SPC3 (PC1/3) suggest that C-domain sequences contribute to cleavage site selection. The structure of proinsulin provides a foundation for studies of insulin biosynthesis and its impairment in monogenic forms of diabetes mellitus.


  • Organizational Affiliation

    Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA. yanwu.yang@case.edu


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Insulin86Homo sapiensMutation(s): 3 
Gene Names: INS
UniProt & NIH Common Fund Data Resources
Find proteins for P01308 (Homo sapiens)
Explore P01308 
Go to UniProtKB:  P01308
PHAROS:  P01308
GTEx:  ENSG00000254647 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01308
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 90 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with acceptable covalent geometry 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-01-26
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-13
    Changes: Data collection, Database references, Derived calculations