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Sugar binding protein, hormone PDB id
3g7v
Jmol
Contents
Protein chains
399 a.a. *
Ligands
MAL ×4
SO4 ×15
GOL ×5
Waters ×862
* Residue conservation analysis
PDB id:
3g7v
Name: Sugar binding protein, hormone
Title: Islet amyloid polypeptide (iapp or amylin) fused to maltose protein
Structure: Maltose-binding periplasmic protein, islet amyloi polypeptide fusion protein. Chain: a, b, c, d. Synonym: mmbp, maltodextrin-binding protein, amylin, diabet associated peptide, dap, insulinoma amyloid peptide. Engineered: yes
Source: Escherichia coli, homo sapiens. Organism_taxid: 83333,9606. Gene: male, b4034, jw3994, iapp. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.86Å     R-factor:   0.178     R-free:   0.205
Authors: J.J.W.Wiltzius,M.R.Sawaya,D.Eisenberg
Key ref: J.J.Wiltzius et al. (2009). Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process. Protein Sci, 18, 1521-1530. PubMed id: 19475663 DOI: 10.1002/pro.145
Date:
10-Feb-09     Release date:   23-Jun-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0AEX9  (MALE_ECOLI) -  Maltose-binding periplasmic protein
Seq:
Struc: 		396 a.a.
399 a.a.*
Protein chains
Pfam   ArchSchema ?
P10997  (IAPP_HUMAN) -  Islet amyloid polypeptide
Seq:
Struc: 		89 a.a.
399 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 38 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   3 terms 
  Biological process     transport   4 terms 
  Biochemical function     transporter activity     5 terms  

 

 
DOI no: 10.1002/pro.145 Protein Sci 18:1521-1530 (2009)
PubMed id: 19475663  
 
 
Atomic structures of IAPP (amylin) fusions suggest a mechanism for fibrillation and the role of insulin in the process.
J.J.Wiltzius, S.A.Sievers, M.R.Sawaya, D.Eisenberg.
 
  ABSTRACT  
 
Islet Amyloid Polypeptide (IAPP or amylin) is a peptide hormone produced and stored in the beta-islet cells of the pancreas along with insulin. IAPP readily forms amyloid fibrils in vitro, and the deposition of fibrillar IAPP has been correlated with the pathology of type II diabetes. The mechanism of the conversion that IAPP undergoes from soluble to fibrillar forms has been unclear. By chaperoning IAPP through fusion to maltose binding protein, we find that IAPP can adopt a alpha-helical structure at residues 8-18 and 22-27 and that molecules of IAPP dimerize. Mutational analysis suggests that this dimerization is on the pathway to fibrillation. The structure suggests how IAPP may heterodimerize with insulin, which we confirmed by protein crosslinking. Taken together, these experiments suggest the helical dimerization of IAPP accelerates fibril formation and that insulin impedes fibrillation by blocking the IAPP dimerization interface.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20028124 P.Cao, F.Meng, A.Abedini, and D.P.Raleigh (2010).
The ability of rodent islet amyloid polypeptide to inhibit amyloid formation by human islet amyloid polypeptide has important implications for the mechanism of amyloid formation and the design of inhibitors.
  Biochemistry, 49, 872-881.  
20630475 P.Marek, S.Mukherjee, M.T.Zanni, and D.P.Raleigh (2010).
Residue-specific, real-time characterization of lag-phase species and fibril growth during amyloid formation: a combined fluorescence and IR study of p-cyanophenylalanine analogs of islet amyloid polypeptide.
  J Mol Biol, 400, 878-888.  
20672280 S.Scalisi, M.F.Sciacca, G.Zhavnerko, D.M.Grasso, G.Marletta, and C.La Rosa (2010).
Self-assembling pathway of HiApp fibrils within lipid bilayers.
  Chembiochem, 11, 1856-1859.  
20043185 U.Hinz, R.Apweiler, M.J.Martin, C.O'Donovan, M.Magrane, Y.Alam-Faruque, R.Antunes, D.Barrell, B.Bely, M.Bingley, D.Binns, L.Bower, P.Browne, W.M.Chan, E.Dimmer, R.Eberhardt, A.Fedotov, R.Foulger, J.Garavelli, R.Huntley, J.Jacobsen, M.Kleen, K.Laiho, R.Leinonen, D.Legge, Q.Lin, W.Liu, J.Luo, S.Orchard, S.Patient, D.Poggioli, M.Pruess, M.Corbett, G.di Martino, M.Donnelly, P.van Rensburg, A.Bairoch, L.Bougueleret, I.Xenarios, S.Altairac, A.Auchincloss, G.Argoud-Puy, K.Axelsen, D.Baratin, M.C.Blatter, B.Boeckmann, J.Bolleman, L.Bollondi, E.Boutet, S.B.Quintaje, L.Breuza, A.Bridge, E.de Castro, L.Ciapina, D.Coral, E.Coudert, I.Cusin, F.David, G.Delbard, M.Doche, D.Dornevil, P.D.Roggli, S.Duvaud, A.Estreicher, L.Famiglietti, M.Feuermann, S.Gehant, N.Farriol-Mathis, S.Ferro, E.Gasteiger, A.Gateau, V.Gerritsen, A.Gos, N.Gruaz-Gumowski, U.Hinz, C.Hulo, N.Hulo, J.James, S.Jimenez, F.Jungo, T.Kappler, G.Keller, C.Lachaize, L.Lane-Guermonprez, P.Langendijk-Genevaux, V.Lara, P.Lemercier, D.Lieberherr, T.d.e. .O.Lima, V.Mangold, X.Martin, P.Masson, M.Moinat, A.Morgat, A.Mottaz, S.Paesano, I.Pedruzzi, S.Pilbout, V.Pillet, and S.Poux (2010).
From protein sequences to 3D-structures and beyond: the example of the UniProt knowledgebase.
  Cell Mol Life Sci, 67, 1049-1064.  
20445236 Z.S.Derewenda (2010).
Application of protein engineering to enhance crystallizability and improve crystal properties.
  Acta Crystallogr D Biol Crystallogr, 66, 604-615.  
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.