PDBsum entry 1iyt

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protein links
Protein binding PDB id
Protein chain
42 a.a. *
* Residue conservation analysis
PDB id:
Name: Protein binding
Title: Solution structure of the alzheimer's disease amyloid beta- peptide (1-42)
Structure: Alzheimer's disease amyloid. Chain: a. Fragment: beta-peptide. Synonym: alzheimer's disease amyloid a4 protein. Engineered: yes
Source: Synthetic: yes. Other_details: the peptide was prepared by solid-phase synthesis. The sequence of the peptide is naturally found in homo sapiens (human).
NMR struc: 10 models
Authors: O.Crescenzi,S.Tomaselli,R.Guerrini,S.Salvadori,A.M.D'Ursi, P.A.Temussi,D.Picone
Key ref:
O.Crescenzi et al. (2002). Solution structure of the Alzheimer amyloid beta-peptide (1-42) in an apolar microenvironment. Similarity with a virus fusion domain. Eur J Biochem, 269, 5642-5648. PubMed id: 12423364 DOI: 10.1046/j.1432-1033.2002.03271.x
06-Sep-02     Release date:   11-Feb-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P05067  (A4_HUMAN) -  Amyloid beta A4 protein
770 a.a.
42 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     integral to membrane   1 term 
  Biological process     nervous system development   1 term 


DOI no: 10.1046/j.1432-1033.2002.03271.x Eur J Biochem 269:5642-5648 (2002)
PubMed id: 12423364  
Solution structure of the Alzheimer amyloid beta-peptide (1-42) in an apolar microenvironment. Similarity with a virus fusion domain.
O.Crescenzi, S.Tomaselli, R.Guerrini, S.Salvadori, A.M.D'Ursi, P.A.Temussi, D.Picone.
The major components of neuritic plaques found in Alzheimer disease (AD) are peptides known as amyloid beta-peptides (Abeta), which derive from the proteolitic cleavage of the amyloid precursor proteins. In vitro Abeta may undergo a conformational transition from a soluble form to aggregated, fibrillary beta-sheet structures, which seem to be neurotoxic. Alternatively, it has been suggested that an alpha-helical form can be involved in a process of membrane poration, which would then trigger cellular death. Conformational studies on these peptides in aqueous solution are complicated by their tendency to aggregate, and only recently NMR structures of Abeta-(1-40) and Abeta-(1-42) have been determined in aqueous trifluoroethanol or in SDS micelles. All these studies hint to the presence of two helical regions, connected through a flexible kink, but it proved difficult to determine the length and position of the helical stretches with accuracy and, most of all, to ascertain whether the kink region has a preferred conformation. In the search for a medium which could allow a more accurate structure determination, we performed an exhaustive solvent scan that showed a high propensity of Abeta-(1-42) to adopt helical conformations in aqueous solutions of fluorinated alcohols. The 3D NMR structure of Abeta-(1-42) shows two helical regions encompassing residues 8-25 and 28-38, connected by a regular type I beta-turn. The surprising similarity of this structure, as well as the sequence of the C-terminal moiety, with those of the fusion domain of influenza hemagglutinin suggests a direct mechanism of neurotoxicity.
  Selected figure(s)  
Figure 5.
Fig. 5. Stereo view of the lowest energy structure colored according to the electrostatic potential.
Figure 6.
Fig. 6. Comparison of the shapes of the lowest energy structure of HA_fd(A) and of the 1–35 region of A -(1–42)(B). Residue side chains are colored according to their hydrophobic character (high = red, low = blue). The sequences of the two peptides, aligned with clustalx[42], are shown in panel (C). Identical residues are reported in green, conserved or semiconserved in yellow.
  The above figures are reprinted by permission from the Federation of European Biochemical Societies: Eur J Biochem (2002, 269, 5642-5648) copyright 2002.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20734314 C.Lee, and S.Ham (2011).
Characterizing amyloid-beta protein misfolding from molecular dynamics simulations with explicit water.
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21371882 C.Wu, and J.E.Shea (2011).
Coarse-grained models for protein aggregation.
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20049499 C.Yang, X.Zhu, J.Li, and R.Shi (2010).
Exploration of the mechanism for LPFFD inhibiting the formation of beta-sheet conformation of A beta(1-42) in water.
  J Mol Model, 16, 813-821.  
20401887 M.Bartolini, and V.Andrisano (2010).
Strategies for the inhibition of protein aggregation in human diseases.
  Chembiochem, 11, 1018-1035.  
20825426 M.L.Bernardi, D.Picone, L.Tuppo, I.Giangrieco, G.Petrella, P.Palazzo, R.Ferrara, M.Tamburrini, A.Mari, and M.A.Ciardiello (2010).
Physico-chemical features of the environment affect the protein conformation and the immunoglobulin E reactivity of kiwellin (Act d 5).
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20027621 S.Tzotzos, and A.J.Doig (2010).
Amyloidogenic sequences in native protein structures.
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20939098 Y.Shafrir, S.Durell, N.Arispe, and H.R.Guy (2010).
Models of membrane-bound Alzheimer's Abeta peptide assemblies.
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20830782 Y.Shafrir, S.R.Durell, A.Anishkin, and H.R.Guy (2010).
Beta-barrel models of soluble amyloid beta oligomers and annular protofibrils.
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19416063 J.A.Hebda, and A.D.Miranker (2009).
The interplay of catalysis and toxicity by amyloid intermediates on lipid bilayers: insights from type II diabetes.
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19995075 N.Miyashita, J.E.Straub, and D.Thirumalai (2009).
Structures of beta-amyloid peptide 1-40, 1-42, and 1-55-the 672-726 fragment of APP-in a membrane environment with implications for interactions with gamma-secretase.
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19023881 P.Juszczyk, A.S.Kołodziejczyk, and Z.Grzonka (2009).
FTIR spectroscopic studies on aggregation process of the beta-amyloid 11-28 fragment and its variants.
  J Pept Sci, 15, 23-29.  
19450490 P.Picone, R.Carrotta, G.Montana, M.R.Nobile, P.L.San Biagio, and M.Di Carlo (2009).
Abeta oligomers and fibrillar aggregates induce different apoptotic pathways in LAN5 neuroblastoma cell cultures.
  Biophys J, 96, 4200-4211.  
19995078 R.P.Nanga, J.R.Brender, S.Vivekanandan, N.Popovych, and A.Ramamoorthy (2009).
NMR structure in a membrane environment reveals putative amyloidogenic regions of the SEVI precursor peptide PAP(248-286).
  J Am Chem Soc, 131, 17972-17979.
PDB code: 2l3h
18479708 B.Tarus, J.E.Straub, and D.Thirumalai (2008).
Structures and free-energy landscapes of the wild type and mutants of the Abeta(21-30) peptide are determined by an interplay between intrapeptide electrostatic and hydrophobic interactions.
  J Mol Biol, 379, 815-829.  
18637027 C.Auvynet, C.El Amri, C.Lacombe, F.Bruston, J.Bourdais, P.Nicolas, and Y.Rosenstein (2008).
Structural requirements for antimicrobial versus chemoattractant activities for dermaseptin S9.
  FEBS J, 275, 4134-4151.  
18390616 D.H.Kim, and J.A.Frangos (2008).
Effects of amyloid beta-peptides on the lysis tension of lipid bilayer vesicles containing oxysterols.
  Biophys J, 95, 620-628.  
18186465 E.Y.Chi, C.Ege, A.Winans, J.Majewski, G.Wu, K.Kjaer, and K.Y.Lee (2008).
Lipid membrane templates the ordering and induces the fibrillogenesis of Alzheimer's disease amyloid-beta peptide.
  Proteins, 72, 1.  
19026086 I.Brovchenko, R.R.Burri, A.Krukau, A.Oleinikova, and R.Winter (2008).
Intrinsic thermal expansivity and hydrational properties of amyloid peptide Abeta42 in liquid water.
  J Chem Phys, 129, 195101.  
18515070 L.M.Gordon, A.Nisthal, A.B.Lee, S.Eskandari, P.Ruchala, C.L.Jung, A.J.Waring, and P.W.Mobley (2008).
Structural and functional properties of peptides based on the N-terminus of HIV-1 gp41 and the C-terminus of the amyloid-beta protein.
  Biochim Biophys Acta, 1778, 2127-2137.  
18228239 M.Valerio, F.Porcelli, J.P.Zbilut, A.Giuliani, C.Manetti, and F.Conti (2008).
pH effects on the conformational preferences of amyloid beta-peptide (1-40) in HFIP aqueous solution by NMR spectroscopy.
  ChemMedChem, 3, 833-843.  
18835397 M.Yang, and D.B.Teplow (2008).
Amyloid beta-protein monomer folding: free-energy surfaces reveal alloform-specific differences.
  J Mol Biol, 384, 450-464.  
18447506 P.Anand, F.S.Nandel, and U.H.Hansmann (2008).
The Alzheimer's beta amyloid (Abeta1-39) monomer in an implicit solvent.
  J Chem Phys, 128, 165102.  
18989932 R.P.Nanga, J.R.Brender, J.Xu, G.Veglia, and A.Ramamoorthy (2008).
Structures of rat and human islet amyloid polypeptide IAPP(1-19) in micelles by NMR spectroscopy.
  Biochemistry, 47, 12689-12697.  
18607649 Y.Mantri, M.Fioroni, and M.H.Baik (2008).
Computational study of the binding of Cu(II) to Alzheimer's amyloid-beta peptide: Do Abeta42 and Abeta40 bind copper in identical fashion?
  J Biol Inorg Chem, 13, 1197-1204.  
17211889 F.Dulin, I.Callebaut, N.Colloc'h, and J.P.Mornon (2007).
Sequence-based modeling of Abeta42 soluble oligomers.
  Biopolymers, 85, 422-437.  
17657567 J.Jarvet, J.Danielsson, P.Damberg, M.Oleszczuk, and A.Gräslund (2007).
Positioning of the Alzheimer Abeta(1-40) peptide in SDS micelles using NMR and paramagnetic probes.
  J Biomol NMR, 39, 63-72.  
17942695 J.Khandogin, and C.L.Brooks (2007).
Linking folding with aggregation in Alzheimer's beta-amyloid peptides.
  Proc Natl Acad Sci U S A, 104, 16880-16885.  
17070840 N.L.Fawzi, Y.Okabe, E.H.Yap, and T.Head-Gordon (2007).
Determining the critical nucleus and mechanism of fibril elongation of the Alzheimer's Abeta(1-40) peptide.
  J Mol Biol, 365, 535-550.  
17534931 S.Rodziewicz-Motowidło, P.Juszczyk, A.S.Kołodziejczyk, E.Sikorska, A.Skwierawska, M.Oleszczuk, and Z.Grzonka (2007).
Conformational solution studies of the SDS micelle-bound 11-28 fragment of two Alzheimer's beta-amyloid variants (E22K and A21G) using CD, NMR, and MD techniques.
  Biopolymers, 87, 23-39.  
16501222 A.Baumketner, S.L.Bernstein, T.Wyttenbach, G.Bitan, D.B.Teplow, M.T.Bowers, and J.E.Shea (2006).
Amyloid beta-protein monomer structure: a computational and experimental study.
  Protein Sci, 15, 420-428.  
16215229 A.Olofsson, A.E.Sauer-Eriksson, and A.Ohman (2006).
The solvent protection of alzheimer amyloid-beta-(1-42) fibrils as determined by solution NMR spectroscopy.
  J Biol Chem, 281, 477-483.  
16294338 D.Flöck, S.Colacino, G.Colombo, and A.Di Nola (2006).
Misfolding of the amyloid beta-protein: a molecular dynamics study.
  Proteins, 62, 183-192.  
16826550 J.Danielsson, A.Andersson, J.Jarvet, and A.Gräslund (2006).
15N relaxation study of the amyloid beta-peptide: structural propensities and persistence length.
  Magn Reson Chem, 44, S114-S121.  
17215879 J.K.Rainey, L.Fliegel, and B.D.Sykes (2006).
Strategies for dealing with conformational sampling in structural calculations of flexible or kinked transmembrane peptides.
  Biochem Cell Biol, 84, 918-929.  
16367755 K.Takano, S.Endo, A.Mukaiyama, H.Chon, H.Matsumura, Y.Koga, and S.Kanaya (2006).
Structure of amyloid beta fragments in aqueous environments.
  FEBS J, 273, 150-158.
PDB code: 1x1p
16731975 M.Bisaglia, A.Trolio, M.Bellanda, E.Bergantino, L.Bubacco, and S.Mammi (2006).
Structure and topology of the non-amyloid-beta component fragment of human alpha-synuclein bound to micelles: implications for the aggregation process.
  Protein Sci, 15, 1408-1416.  
17052343 R.H.Ashley, T.A.Harroun, T.Hauss, K.C.Breen, and J.P.Bradshaw (2006).
Autoinsertion of soluble oligomers of Alzheimer's Abeta(1-42) peptide into cholesterol-containing membranes is accompanied by relocation of the sterol towards the bilayer surface.
  BMC Struct Biol, 6, 21.  
16444756 S.Tomaselli, V.Esposito, P.Vangone, N.A.van Nuland, A.M.Bonvin, R.Guerrini, T.Tancredi, P.A.Temussi, and D.Picone (2006).
The alpha-to-beta conformational transition of Alzheimer's Abeta-(1-42) peptide in aqueous media is reversible: a step by step conformational analysis suggests the location of beta conformation seeding.
  Chembiochem, 7, 257-267.
PDB code: 1z0q
15557279 D.V.Laurents, P.M.Gorman, M.Guo, M.Rico, A.Chakrabartty, and M.Bruix (2005).
Alzheimer's Abeta40 studied by NMR at low pH reveals that sodium 4,4-dimethyl-4-silapentane-1-sulfonate (DSS) binds and promotes beta-ball oligomerization.
  J Biol Chem, 280, 3675-3685.  
  15639796 G.C.Gregory, and G.M.Halliday (2005).
What is the dominant Abeta species in human brain tissue? A review.
  Neurotox Res, 7, 29-41.  
15615707 J.Thimm, A.Mechler, H.Lin, S.Rhee, and R.Lal (2005).
Calcium-dependent open/closed conformations and interfacial energy maps of reconstituted hemichannels.
  J Biol Chem, 280, 10646-10654.  
16339896 L.Cruz, B.Urbanc, J.M.Borreguero, N.D.Lazo, D.B.Teplow, and H.E.Stanley (2005).
Solvent and mutation effects on the nucleation of amyloid beta-protein folding.
  Proc Natl Acad Sci U S A, 102, 18258-18263.  
15475582 L.Vaccaro, K.J.Cross, J.Kleinjung, S.K.Straus, D.J.Thomas, S.A.Wharton, J.J.Skehel, and F.Fraternali (2005).
Plasticity of influenza haemagglutinin fusion peptides and their interaction with lipid bilayers.
  Biophys J, 88, 25-36.  
15985437 R.Carrotta, M.Manno, D.Bulone, V.Martorana, and P.L.San Biagio (2005).
Protofibril formation of amyloid beta-protein at low pH via a non-cooperative elongation mechanism.
  J Biol Chem, 280, 30001-30008.  
16650066 S.Parry, D.Todorova-Balvay, T.Srikrishnan, and E.Sulkowski (2005).
Thiophilic interaction chromatography of Alzheimer's beta-amyloid peptides.
  J Pept Res, 66, 99.  
15454432 B.Urbanc, L.Cruz, F.Ding, D.Sammond, S.Khare, S.V.Buldyrev, H.E.Stanley, and N.V.Dokholyan (2004).
Molecular dynamics simulation of amyloid beta dimer formation.
  Biophys J, 87, 2310-2321.  
15583128 B.Urbanc, L.Cruz, S.Yun, S.V.Buldyrev, G.Bitan, D.B.Teplow, and H.E.Stanley (2004).
In silico study of amyloid beta-protein folding and oligomerization.
  Proc Natl Acad Sci U S A, 101, 17345-17350.  
15649580 C.Morgan, M.Colombres, M.T.Nuñez, and N.C.Inestrosa (2004).
Structure and function of amyloid in Alzheimer's disease.
  Prog Neurobiol, 74, 323-349.  
15234966 I.Qahwash, W.He, A.Tomasselli, R.F.Kletzien, and R.Yan (2004).
Processing amyloid precursor protein at the beta-site requires proper orientation to be accessed by BACE1.
  J Biol Chem, 279, 39010-39016.  
12554637 P.A.Temussi, L.Masino, and A.Pastore (2003).
From Alzheimer to Huntington: why is a structural understanding so difficult?
  EMBO J, 22, 355-361.  
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.