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PDBsum entry 3dxe

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protein Protein-protein interface(s) links
Protein binding PDB id
3dxe
Jmol
Contents
Protein chains
124 a.a. *
27 a.a. *
Waters ×236
* Residue conservation analysis
PDB id:
3dxe
Name: Protein binding
Title: Crystal structure of the intracellular domain of human app (t668a mutant) in complex with fe65-ptb2
Structure: Amyloid beta a4 protein-binding family b member 1. Chain: a, c. Fragment: ptb2 domain, unp residues 534-667. Engineered: yes. Amyloid beta a4 protein. Chain: b, d. Fragment: app intracellular domain, unp residues 739-770. Engineered: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: apbb1, fe65, rir. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: app, a4, ad1.
Resolution:
2.00Å     R-factor:   0.208     R-free:   0.241
Authors: J.Radzimanowski,I.Sinning,K.Wild
Key ref: J.Radzimanowski et al. (2008). Structure of the intracellular domain of the amyloid precursor protein in complex with Fe65-PTB2. EMBO Rep, 9, 1134-1140. PubMed id: 18833287
Date:
24-Jul-08     Release date:   16-Sep-08    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
O00213  (APBB1_HUMAN) -  Amyloid beta A4 precursor protein-binding family B member 1
Seq:
Struc:
 
Seq:
Struc:
710 a.a.
124 a.a.
Protein chains
Pfam   ArchSchema ?
P05067  (A4_HUMAN) -  Amyloid beta A4 protein
Seq:
Struc:
 
Seq:
Struc:
770 a.a.
27 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     nervous system development   1 term 

 

 
EMBO Rep 9:1134-1140 (2008)
PubMed id: 18833287  
 
 
Structure of the intracellular domain of the amyloid precursor protein in complex with Fe65-PTB2.
J.Radzimanowski, B.Simon, M.Sattler, K.Beyreuther, I.Sinning, K.Wild.
 
  ABSTRACT  
 
Cleavage of the amyloid precursor protein (APP) is a crucial event in Alzheimer disease pathogenesis that creates the amyloid-beta peptide (Abeta) and liberates the carboxy-terminal APP intracellular domain (AICD) into the cytosol. The interaction of the APP C terminus with the adaptor protein Fe65 mediates APP trafficking and signalling, and is thought to regulate APP processing and Abeta generation. We determined the crystal structure of the AICD in complex with the C-terminal phosphotyrosine-binding (PTB) domain of Fe65. The unique interface involves the NPxY PTB-binding motif and two alpha helices. The amino-terminal helix of the AICD is capped by threonine T(668), an Alzheimer disease-relevant phosphorylation site involved in Fe65-binding regulation. The structure together with mutational studies, isothermal titration calorimetry and nuclear magnetic resonance experiments sets the stage for understanding T(668) phosphorylation-dependent complex regulation at a molecular level. A molecular switch model is proposed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21512128 R.Ghai, M.Mobli, S.J.Norwood, A.Bugarcic, R.D.Teasdale, G.F.King, and B.M.Collins (2011).
Phox homology band 4.1/ezrin/radixin/moesin-like proteins function as molecular scaffolds that interact with cargo receptors and Ras GTPases.
  Proc Natl Acad Sci U S A, 108, 7763-7768.
PDB code: 3lui
20568118 O.Y.Kwon, K.Hwang, J.A.Kim, K.Kim, I.C.Kwon, H.K.Song, and H.Jeon (2010).
Dab1 binds to Fe65 and diminishes the effect of Fe65 or LRP1 on APP processing.
  J Cell Biochem, 111, 508-519.  
20213668 R.J.Falconer, A.Penkova, I.Jelesarov, and B.M.Collins (2010).
Survey of the year 2008: applications of isothermal titration calorimetry.
  J Mol Recognit, 23, 395-413.  
19333550 K.T.Jacobsen, and K.Iverfeldt (2009).
Amyloid precursor protein and its homologues: a family of proteolysis-dependent receptors.
  Cell Mol Life Sci, 66, 2299-2318.  
20076770 V.Muresan, and Z.Muresan (2009).
Is abnormal axonal transport a cause, a contributing factor or a consequence of the neuronal pathology in Alzheimer's disease?
  Future Neurol, 4, 761-773.  
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.