2AIY

R6 HUMAN INSULIN HEXAMER (SYMMETRIC), NMR, 20 STRUCTURES


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 40 
  • Conformers Submitted: 20 
  • Selection Criteria: LOWEST TOTAL ENERGY 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Unraveling the symmetry ambiguity in a hexamer: calculation of the R6 human insulin structure.

O'Donoghue, S.I.Chang, X.Abseher, R.Nilges, M.Led, J.J.

(2000) J Biomol NMR 16: 93-108

  • DOI: https://doi.org/10.1023/a:1008323819099
  • Primary Citation of Related Structures:  
    2AIY, 3AIY, 4AIY, 5AIY

  • PubMed Abstract: 

    Crystallographic and NMR studies of insulin have revealed a highly flexible molecule with a range of different aggregation and structural states; the importance of these states for the function of the hormone is still unclear. To address this question, we have studied the solution structure of the insulin R6 symmetric hexamer using NMR spectroscopy. Structure determination of symmetric oligomers by NMR is complicated due to 'symmetry ambiguity' between intra- and intermonomer NOEs, and between different classes of intermonomer NOEs. Hence, to date, only two symmetric tetramers and one symmetric pentamer (VTB, B subunit of verotoxin) have been solved by NMR: there has been no other symmetric hexamer or higher-order oligomer. Recently, we reported a solution structure for R6 insulin hexamer. However, in that study, a crystal structure was used as a reference to resolve ambiguities caused by the threefold symmetry; the same method was used in solving VTB. Here, we have successfully recalculated R6 insulin using the symmetry-ADR method, a computational strategy in which ambiguities are resolved using the NMR data alone. Thus the obtained structure is a refinement of the previous R6 solution structure. Correlated motions in the final structural ensemble were analysed using a recently developed principal component method; this suggests the presence of two major conformational substates. The study demonstrates that the solution structure of higher-order symmetric oligomers can be determined unambiguously from NMR data alone, using the symmetry-ADR method. This success bodes well for future NMR studies of higher-order symmetric oligomers. The correlated motions observed in the structural ensemble suggest a new insight into the mechanism of phenol exchange and the T6 <--> R6 transition of insulin in solution.


  • Organizational Affiliation

    European Molecular Biology Laboratory, Heidelberg, Germany.


Macromolecules

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN (INSULIN)
A, C, E, G, I
A, C, E, G, I, K
21N/AMutation(s): 0 
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
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN (INSULIN)
B, D, F, H, J
B, D, F, H, J, L
30N/AMutation(s): 0 
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
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 40 
  • Conformers Submitted: 20 
  • Selection Criteria: LOWEST TOTAL ENERGY 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-02-28
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-03-09
    Changes: Database references, Derived calculations
  • Version 1.4: 2023-12-27
    Changes: Data collection