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PDBsum entry 3aiy

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protein ligands Protein-protein interface(s) links
Hormone/growth factor PDB id
3aiy
Jmol
Contents
Protein chains
(+ 0 more) 21 a.a.
(+ 0 more) 30 a.a. *
Ligands
IPH ×6
* Residue conservation analysis
PDB id:
3aiy
Name: Hormone/growth factor
Title: R6 human insulin hexamer (symmetric), nmr, refined average structure
Structure: Protein (insulin). Chain: a, c, e, g, i, k. Fragment: alpha chain. Engineered: yes. Other_details: a phenol molecule is non-covalently attached to each insulin monomer. Protein (insulin). Chain: b, d, f, h, j, l. Fragment: beta chain.
Source: Synthetic: yes. Other_details: the protein was chemically synthesized from the secretion of human (homo sapiens) pancreatic cells.. The secretion of human (homo sapiens) pancreatic cells.
NMR struc: 1 models
Authors: S.I.O'Donoghue,X.Chang,R.Abseher,M.Nilges,J.J.Led
Key ref: S.I.O'Donoghue et al. (2000). Unraveling the symmetry ambiguity in a hexamer: calculation of the R6 human insulin structure. J Biomol NMR, 16, 93. PubMed id: 10723989
Date:
29-Dec-98     Release date:   28-Feb-00    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
Seq:
Struc:
110 a.a.
21 a.a.
Protein chains
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
Seq:
Struc:
110 a.a.
30 a.a.
Key:    PfamA domain  Secondary structure

 

 
J Biomol NMR 16:93 (2000)
PubMed id: 10723989  
 
 
Unraveling the symmetry ambiguity in a hexamer: calculation of the R6 human insulin structure.
S.I.O'Donoghue, X.Chang, R.Abseher, M.Nilges, J.J.Led.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
18951392 B.Bardiaux, A.Bernard, W.Rieping, M.Habeck, T.E.Malliavin, and M.Nilges (2009).
Influence of different assignment conditions on the determination of symmetric homodimeric structures with ARIA.
  Proteins, 75, 569-585.  
18831040 C.A.Laughton, M.Orozco, and W.Vranken (2009).
COCO: a simple tool to enrich the representation of conformational variability in NMR structures.
  Proteins, 75, 206-216.  
18676643 H.Vashisth, and C.F.Abrams (2008).
Ligand escape pathways and (un)binding free energy calculations for the hexameric insulin-phenol complex.
  Biophys J, 95, 4193-4204.  
17192589 S.Potluri, A.K.Yan, B.R.Donald, and C.Bailey-Kellogg (2007).
A complete algorithm to resolve ambiguity for intersubunit NOE assignment in structure determination of symmetric homo-oligomers.
  Protein Sci, 16, 69-81.  
17269119 T.Inaba, and F.Sato (2007).
Development of parallel density functional program using distributed matrix to calculate all-electron canonical wavefunction of large molecules.
  J Comput Chem, 28, 984-995.  
16845606 J.Shafqat, E.Melles, K.Sigmundsson, B.L.Johansson, K.Ekberg, G.Alvelius, M.Henriksson, J.Johansson, J.Wahren, and H.Jörnvall (2006).
Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects.
  Cell Mol Life Sci, 63, 1805-1811.  
16897780 S.Potluri, A.K.Yan, J.J.Chou, B.R.Donald, and C.Bailey-Kellogg (2006).
Structure determination of symmetric homo-oligomers by a complete search of symmetry configuration space, using NMR restraints and van der Waals packing.
  Proteins, 65, 203-219.
PDB code: 2hyn
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.