PDBsum entry 2ela

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protein Protein-protein interface(s) links
Cell cycle PDB id
Protein chains
131 a.a. *
141 a.a. *
Waters ×236
* Residue conservation analysis
PDB id:
Name: Cell cycle
Title: Crystal structure of the ptb domain of human appl1
Structure: Adapter protein containing ph domain, ptb domain and leucine zipper motif 1. Chain: a, b. Fragment: ptb domain. Synonym: appl1, dip13 alpha, dcc-interacting protein 13 alpha. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.00Å     R-factor:   0.222     R-free:   0.259
Authors: J.Li,X.Mao,L.Q.Dong,F.Liu,L.Tong
Key ref:
J.Li et al. (2007). Crystal Structures of the BAR-PH and PTB Domains of Human APPL1. Structure, 15, 525-533. PubMed id: 17502098 DOI: 10.1016/j.str.2007.03.011
27-Mar-07     Release date:   29-May-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9UKG1  (DP13A_HUMAN) -  DCC-interacting protein 13-alpha
709 a.a.
131 a.a.
Protein chain
Pfam   ArchSchema ?
Q9UKG1  (DP13A_HUMAN) -  DCC-interacting protein 13-alpha
709 a.a.
141 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1016/j.str.2007.03.011 Structure 15:525-533 (2007)
PubMed id: 17502098  
Crystal Structures of the BAR-PH and PTB Domains of Human APPL1.
J.Li, X.Mao, L.Q.Dong, F.Liu, L.Tong.
APPL1 interacts with adiponectin receptors and other important signaling molecules. It contains a BAR and a PH domain near its N terminus, and the two domains may function as a unit (BAR-PH domain). We report here the crystal structures of the BAR-PH and PTB domains of human APPL1. The structures reveal novel features for BAR domain dimerization and for the interactions between the BAR and PH domains. The BAR domain dimer of APPL1 contains two four-helical bundles, whereas other BAR domain dimers have only three helices in each bundle. The PH domain is located at the opposite ends of the BAR domain dimer. Yeast two-hybrid assays confirm the interactions between the BAR and PH domains. Lipid binding assays show that the BAR, PH, and PTB domains can bind phospholipids. The ability of APPL1 to interact with multiple signaling molecules and phospholipids supports an important role for this adaptor in cell signaling.
  Selected figure(s)  
Figure 2.
Figure 2. Structure of the BAR-PH Domain Dimer of Human APPL1
(A) Schematic representation of the BAR-PH domain dimer. One monomer is shown in yellow and the other in cyan.
(B) The dimer after 90° rotation around the horizontal axis, showing the banana shape of the structure. The red star indicates the location of the β1-β2 loop in the PH domain, which is near the putative phospholipid binding site.
(C) Superposition of the APPL1 BAR domain dimer (in yellow and cyan) and that of endophilin (in gray). The red arrow highlights the structural differences between the two dimers. Produced with PyMOL (DeLano, 2002).
Figure 4.
Figure 4. Molecular Surface of the BAR-PH Domain of APPL1
(A) The side view of the molecular surface of the BAR-PH domain. Strictly conserved basic residues are colored in dark blue, and basic residues conserved only in APPL1 and APPL2 are in light blue. The diameter of the BAR-PH dimer is about 170 Å.
(B) The top view of the molecular surface of the BAR-PH domain. There is a cluster of positively charged residues near the BAR-PH interface. Produced with PyMOL (DeLano, 2002).
  The above figures are reprinted by permission from Cell Press: Structure (2007, 15, 525-533) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20814572 H.J.Chial, P.Lenart, and Y.Q.Chen (2010).
APPL proteins FRET at the BAR: direct observation of APPL1 and APPL2 BAR domain-mediated interactions on cell membranes using FRET microscopy.
  PLoS One, 5, e12471.  
20083215 M.Masuda, and N.Mochizuki (2010).
Structural characteristics of BAR domain superfamily to sculpt the membrane.
  Semin Cell Dev Biol, 21, 391-398.  
20095645 R.L.Gant-Branum, J.A.Broussard, A.Mahsut, D.J.Webb, and J.A.McLean (2010).
Identification of phosphorylation sites within the signaling adaptor APPL1 by mass spectrometry.
  J Proteome Res, 9, 1541-1548.  
20040596 Y.Tan, H.You, C.Wu, D.A.Altomare, and J.R.Testa (2010).
Appl1 is dispensable for mouse development, and loss of Appl1 has growth factor-selective effects on Akt signaling in murine embryonic fibroblasts.
  J Biol Chem, 285, 6377-6389.  
19150238 J.Saarikangas, H.Zhao, A.Pykäläinen, P.Laurinmäki, P.K.Mattila, P.K.Kinnunen, S.J.Butcher, and P.Lappalainen (2009).
Molecular mechanisms of membrane deformation by I-BAR domain proteins.
  Curr Biol, 19, 95.  
19416712 K.K.Cheng, M.A.Iglesias, K.S.Lam, Y.Wang, G.Sweeney, W.Zhu, P.M.Vanhoutte, E.W.Kraegen, and A.Xu (2009).
APPL1 potentiates insulin-mediated inhibition of hepatic glucose production and alleviates diabetes via Akt activation in mice.
  Cell Metab, 9, 417-427.  
19303853 R.Zoncu, R.M.Perera, D.M.Balkin, M.Pirruccello, D.Toomre, and P.De Camilli (2009).
A phosphoinositide switch controls the maturation and signaling properties of APPL endosomes.
  Cell, 136, 1110-1121.  
19433865 S.Rashid, I.Pilecka, A.Torun, M.Olchowik, B.Bielinska, and M.Miaczynska (2009).
Endosomal Adaptor Proteins APPL1 and APPL2 Are Novel Activators of {beta}-Catenin/TCF-mediated Transcription.
  J Biol Chem, 284, 18115-18128.  
18854421 S.S.Deepa, and L.Q.Dong (2009).
APPL1: role in adiponectin signaling and beyond.
  Am J Physiol Endocrinol Metab, 296, E22-E36.  
19575675 Y.Shibata, J.Hu, M.M.Kozlov, and T.A.Rapoport (2009).
Mechanisms shaping the membranes of cellular organelles.
  Annu Rev Cell Dev Biol, 25, 329-354.  
18329367 A.Frost, R.Perera, A.Roux, K.Spasov, O.Destaing, E.H.Egelman, P.De Camilli, and V.M.Unger (2008).
Structural basis of membrane invagination by F-BAR domains.
  Cell, 132, 807-817.  
17948057 O.Pylypenko, R.Lundmark, E.Rasmuson, S.R.Carlsson, and A.Rak (2007).
The PX-BAR membrane-remodeling unit of sorting nexin 9.
  EMBO J, 26, 4788-4800.
PDB codes: 2rai 2raj 2rak
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 codes are shown on the right.