PDBsum entry 1x11

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protein Protein-protein interface(s) links
Complex (peptide binding module/peptide) PDB id
Protein chains
135 a.a. *
12 a.a. *
122 a.a. *
13 a.a. *
Waters ×483
* Residue conservation analysis
PDB id:
Name: Complex (peptide binding module/peptide)
Title: X11 ptb domain
Structure: X11. Chain: a, b. Fragment: ptb domain. Engineered: yes. 13-mer peptide. Chain: c, d. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Dimer (from PQS)
2.50Å     R-factor:   0.214     R-free:   0.304
Authors: C.-H.Lee,Z.Zhang,J.Kuriyan
Key ref:
Z.Zhang et al. (1997). Sequence-specific recognition of the internalization motif of the Alzheimer's amyloid precursor protein by the X11 PTB domain. EMBO J, 16, 6141-6150. PubMed id: 9321393 DOI: 10.1093/emboj/16.20.6141
28-Jul-97     Release date:   14-Jan-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q02410  (APBA1_HUMAN) -  Amyloid beta A4 precursor protein-binding family A member 1
837 a.a.
135 a.a.*
Protein chain
Pfam   ArchSchema ?
P05067  (A4_HUMAN) -  Amyloid beta A4 protein
770 a.a.
12 a.a.
Protein chain
Pfam   ArchSchema ?
Q02410  (APBA1_HUMAN) -  Amyloid beta A4 precursor protein-binding family A member 1
837 a.a.
122 a.a.*
Protein chain
Pfam   ArchSchema ?
P05067  (A4_HUMAN) -  Amyloid beta A4 protein
770 a.a.
13 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)


DOI no: 10.1093/emboj/16.20.6141 EMBO J 16:6141-6150 (1997)
PubMed id: 9321393  
Sequence-specific recognition of the internalization motif of the Alzheimer's amyloid precursor protein by the X11 PTB domain.
Z.Zhang, C.H.Lee, V.Mandiyan, J.P.Borg, B.Margolis, J.Schlessinger, J.Kuriyan.
The crystal structure of the phosphotyrosine-binding domain (PTB) of the X11 protein has been determined, in complex with unphosphorylated peptides corresponding to a region of beta-amyloid precursor protein (betaAPP) that is required for receptor internalization. The mode of binding to X11 of the unphosphorylated peptides, which contain an NPxY motif, resembles that of phosphorylated peptides bound to the Shc and IRS-1 PTB domains. Eight peptide residues make specific contacts with the X11 PTB domain, and they collectively achieve high affinity (KD = 0.32 microM) and specificity. These results suggest that, in contrast to the SH2 domains, the PTB domains are primarily peptide-binding domains that have, in some cases, acquired specificity for phosphorylated tyrosines.
  Selected figure(s)  
Figure 3.
Figure 3 Schematic depiction of contacts between the APP peptide and the X11 PTB domain. The strands are shaded green and orange for the PTB domain and the peptide, respectively. Hydrogen bonds are shown as dotted lines, and the distance between the atom attached to the donor hydrogen and the acceptor is shown (in ) for the 10-residue (above the lines) and the 14-residue (in parentheses, below the lines) peptide complexes.
Figure 5.
Figure 5 Comparison of phosphotyrosine/tyrosine-binding sites of the X11 PTB domain and the Src SH2 domain. (A) Molecular surface of the X11 PTB domain, showing the binding site for the tyrosine (+0) and the C-terminal region of the peptide. The polypeptide backbones of the bound peptide and the X11 PTB domain are shown in red and blue tubes, respectively. Also shown are three basic residues (Lys 346, Arg431 and Arg432; removed from surface calculation) of the X11 PTB domain that are potentially involved in phosphotyrosine-binding. The sidechains of Phe(+2) and Phe(+3) of the peptide (colored in yellow) pack against the sidechains of Tyr483 and Phe 486 of the X11 PTB domain (colored in gold). (B) Molecular surface of an unliganded Src SH2 domain (Waksman et al., 1993) showing the deeply buried Arg B5 sidechain (not included in surface calculation). For reference, the structure of a high affinity phosphopeptide is also shown (colored in gold), taken from the pYEEI/Src complex (Waksman et al., 1993). The polypeptide backbone of the Src SH2 domain is shown in purple tubes.
  The above figures are reprinted from an Open Access publication published by Macmillan Publishers Ltd: EMBO J (1997, 16, 6141-6150) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  20378958 J.C.Mitchell, M.S.Perkinton, D.M.Yates, K.F.Lau, B.Rogelj, C.C.Miller, and D.M.McLoughlin (2010).
Expression of the neuronal adaptor protein X11alpha protects against memory dysfunction in a transgenic mouse model of Alzheimer's disease.
  J Alzheimers Dis, 20, 31-36.  
19222704 M.Sakuma, E.Tanaka, H.Taru, S.Tomita, S.Gandy, A.C.Nairn, T.Nakaya, T.Yamamoto, and T.Suzuki (2009).
Phosphorylation of the amino-terminal region of X11L regulates its interaction with APP.
  J Neurochem, 109, 465-475.  
19265194 Y.Zhang, Y.G.Wang, Q.Zhang, X.J.Liu, X.Liu, L.Jiao, W.Zhu, Z.H.Zhang, X.L.Zhao, and C.He (2009).
Interaction of Mint2 with TrkA Is Involved in Regulation of Nerve Growth Factor-induced Neurite Outgrowth.
  J Biol Chem, 284, 12469-12479.  
19726636 Z.Wang, B.Wang, L.Yang, Q.Guo, N.Aithmitti, Z.Songyang, and H.Zheng (2009).
Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis.
  J Neurosci, 29, 10788-10801.  
18650440 H.Li, S.Koshiba, F.Hayashi, N.Tochio, T.Tomizawa, T.Kasai, T.Yabuki, Y.Motoda, T.Harada, S.Watanabe, M.Inoue, Y.Hayashizaki, A.Tanaka, T.Kigawa, and S.Yokoyama (2008).
Structure of the C-terminal phosphotyrosine interaction domain of Fe65L1 complexed with the cytoplasmic tail of amyloid precursor protein reveals a novel peptide binding mode.
  J Biol Chem, 283, 27165-27178.
PDB codes: 1wgu 2roz 2ysz 2yt0 2yt1
18833287 J.Radzimanowski, B.Simon, M.Sattler, K.Beyreuther, I.Sinning, and K.Wild (2008).
Structure of the intracellular domain of the amyloid precursor protein in complex with Fe65-PTB2.
  EMBO Rep, 9, 1134-1140.
PDB codes: 3dxc 3dxd 3dxe
18550529 J.Radzimanowski, S.Ravaud, S.Schlesinger, J.Koch, K.Beyreuther, I.Sinning, and K.Wild (2008).
Crystal structure of the human Fe65-PTB1 domain.
  J Biol Chem, 283, 23113-23120.
PDB codes: 3d8d 3d8e 3d8f
17959829 P.Shrivastava-Ranjan, V.Faundez, G.Fang, H.Rees, J.J.Lah, A.I.Levey, and R.A.Kahn (2008).
Mint3/X11{gamma} Is an ADP-Ribosylation Factor-dependent Adaptor that Regulates the Traffic of the Alzheimer's Precursor Protein from the Trans-Golgi Network.
  Mol Biol Cell, 19, 51-64.  
17473008 C.J.McCleverty, D.C.Lin, and R.C.Liddington (2007).
Structure of the PTB domain of tensin1 and a model for its recruitment to fibrillar adhesions.
  Protein Sci, 16, 1223-1229.
PDB code: 1wvh
16944319 G.Verdile, S.E.Gandy, and R.N.Martins (2007).
The role of presenilin and its interacting proteins in the biogenesis of Alzheimer's beta amyloid.
  Neurochem Res, 32, 609-623.  
17502098 J.Li, X.Mao, L.Q.Dong, F.Liu, and L.Tong (2007).
Crystal structures of the BAR-PH and PTB domains of human APPL1.
  Structure, 15, 525-533.
PDB codes: 2ela 2elb
16764936 B.Rogelj, J.C.Mitchell, C.C.Miller, and D.M.McLoughlin (2006).
The X11/Mint family of adaptor proteins.
  Brain Res Rev, 52, 305-315.  
16982700 M.J.Smith, W.R.Hardy, J.M.Murphy, N.Jones, and T.Pawson (2006).
Screening for PTB domain binding partners and ligand specificity using proteome-derived NPXY peptide arrays.
  Mol Cell Biol, 26, 8461-8474.  
15959902 A.C.Roque, and C.R.Lowe (2005).
Lessons from nature: On the molecular recognition elements of the phosphoprotein binding-domains.
  Biotechnol Bioeng, 91, 546-555.  
16377899 A.Lamberti, O.Longo, P.Del Vecchio, N.Zambrano, G.Barone, T.Russo, and P.Arcari (2005).
Probing the secondary structure of a recombinant neuronal adaptor protein and its phosphotyrosine binding domains.
  Biosci Biotechnol Biochem, 69, 2395-2400.  
16033433 B.Lambson, V.Nene, M.Obura, T.Shah, P.Pandit, O.Ole-Moiyoi, K.Delroux, S.Welburn, R.Skilton, Villiers, and R.Bishop (2005).
Identification of candidate sialome components expressed in ixodid tick salivary glands using secretion signal complementation in mammalian cells.
  Insect Mol Biol, 14, 403-414.  
16252002 C.Reinhard, S.S.Hébert, and B.De Strooper (2005).
The amyloid-beta precursor protein: integrating structure with biological function.
  EMBO J, 24, 3996-4006.  
16007100 J.F.Long, W.Feng, R.Wang, L.N.Chan, F.C.Ip, J.Xia, N.Y.Ip, and M.Zhang (2005).
Autoinhibition of X11/Mint scaffold proteins revealed by the closed conformation of the PDZ tandem.
  Nat Struct Mol Biol, 12, 722-728.
PDB codes: 1u37 1u38 1u39 1u3b
15672415 M.L.Kerr, and D.H.Small (2005).
Cytoplasmic domain of the beta-amyloid protein precursor of Alzheimer's disease: function, regulation of proteolysis, and implications for drug development.
  J Neurosci Res, 80, 151-159.  
15347685 J.H.Lee, K.F.Lau, M.S.Perkinton, C.L.Standen, B.Rogelj, A.Falinska, D.M.McLoughlin, and C.C.Miller (2004).
The neuronal adaptor protein X11beta reduces amyloid beta-protein levels and amyloid plaque formation in the brains of transgenic mice.
  J Biol Chem, 279, 49099-49104.  
12906822 A.Farooq, L.Zeng, K.S.Yan, K.S.Ravichandran, and M.M.Zhou (2003).
Coupling of folding and binding in the PTB domain of the signaling protein Shc.
  Structure, 11, 905-913.
PDB codes: 1n3h 1oy2
12547917 A.Ho, W.Morishita, R.E.Hammer, R.C.Malenka, and T.C.Sudhof (2003).
A role for Mints in transmitter release: Mint 1 knockout mice exhibit impaired GABAergic synaptic transmission.
  Proc Natl Acad Sci U S A, 100, 1409-1414.  
12435749 A.Q.Sun, R.Salkar, Sachchidanand, S.Xu, L.Zeng, M.M.Zhou, and F.J.Suchy (2003).
A 14-amino acid sequence with a beta-turn structure is required for apical membrane sorting of the rat ileal bile acid transporter.
  J Biol Chem, 278, 4000-4009.  
12606711 D.A.Calderwood, Y.Fujioka, Pereda, B.García-Alvarez, T.Nakamoto, B.Margolis, C.J.McGlade, R.C.Liddington, and M.H.Ginsberg (2003).
Integrin beta cytoplasmic domain interactions with phosphotyrosine-binding domains: a structural prototype for diversity in integrin signaling.
  Proc Natl Acad Sci U S A, 100, 2272-2277.  
12970358 J.H.Lee, K.F.Lau, M.S.Perkinton, C.L.Standen, S.J.Shemilt, L.Mercken, J.D.Cooper, D.M.McLoughlin, and C.C.Miller (2003).
The neuronal adaptor protein X11alpha reduces Abeta levels in the brains of Alzheimer's APPswe Tg2576 transgenic mice.
  J Biol Chem, 278, 47025-47029.  
12554651 K.Hamada, T.Shimizu, S.Yonemura, S.Tsukita, S.Tsukita, and T.Hakoshima (2003).
Structural basis of adhesion-molecule recognition by ERM proteins revealed by the crystal structure of the radixin-ICAM-2 complex.
  EMBO J, 22, 502-514.
PDB code: 1j19
12842896 K.Hill, Y.Li, M.Bennett, M.McKay, X.Zhu, J.Shern, E.Torre, J.J.Lah, A.I.Levey, and R.A.Kahn (2003).
Munc18 interacting proteins: ADP-ribosylation factor-dependent coat proteins that regulate the traffic of beta-Alzheimer's precursor protein.
  J Biol Chem, 278, 36032-36040.  
12826668 M.Yun, L.Keshvara, C.G.Park, Y.M.Zhang, J.B.Dickerson, J.Zheng, C.O.Rock, T.Curran, and H.W.Park (2003).
Crystal structures of the Dab homology domains of mouse disabled 1 and 2.
  J Biol Chem, 278, 36572-36581.
PDB codes: 1m7e 1oqn 1p3r
12737822 P.C.Stolt, H.Jeon, H.K.Song, J.Herz, M.J.Eck, and S.C.Blacklow (2003).
Origins of peptide selectivity and phosphoinositide binding revealed by structures of disabled-1 PTB domain complexes.
  Structure, 11, 569-579.
PDB codes: 1ntv 1nu2
12084708 C.Russo, V.Dolcini, S.Salis, V.Venezia, N.Zambrano, T.Russo, and G.Schettini (2002).
Signal transduction through tyrosine-phosphorylated C-terminal fragments of amyloid precursor protein via an enhanced interaction with Shc/Grb2 adaptor proteins in reactive astrocytes of Alzheimer's disease brain.
  J Biol Chem, 277, 35282-35288.  
12016213 C.S.Ho, V.Marinescu, M.L.Steinhilb, J.R.Gaut, R.S.Turner, and E.L.Stuenkel (2002).
Synergistic effects of Munc18a and X11 proteins on amyloid precursor protein metabolism.
  J Biol Chem, 277, 27021-27028.  
11932255 D.A.Calderwood, B.Yan, Pereda, B.G.Alvarez, Y.Fujioka, R.C.Liddington, and M.H.Ginsberg (2002).
The phosphotyrosine binding-like domain of talin activates integrins.
  J Biol Chem, 277, 21749-21758.  
11741908 D.D.Chang, B.Q.Hoang, J.Liu, and T.A.Springer (2002).
Molecular basis for interaction between Icap1 alpha PTB domain and beta 1 integrin.
  J Biol Chem, 277, 8140-8145.
PDB code: 1k11
12221107 G.He, S.Gupta, M.Yi, P.Michaely, H.H.Hobbs, and J.C.Cohen (2002).
ARH is a modular adaptor protein that interacts with the LDL receptor, clathrin, and AP-2.
  J Biol Chem, 277, 44044-44049.  
11877385 K.S.Yan, M.Kuti, S.Yan, S.Mujtaba, A.Farooq, M.P.Goldfarb, and M.M.Zhou (2002).
FRS2 PTB domain conformation regulates interactions with divergent neurotrophic receptors.
  J Biol Chem, 277, 17088-17094.  
11994738 M.B.Yaffe (2002).
Phosphotyrosine-binding domains in signal transduction.
  Nat Rev Mol Cell Biol, 3, 177-186.  
12454490 N.Shi, W.Zhou, K.Tang, Y.Gao, J.Jin, F.Gao, X.Peng, M.Bartlam, B.Qiang, J.Yuan, and Z.Rao (2002).
Expression, crystallization and preliminary X-ray studies of the recombinant PTB domain of human dok-5 protein.
  Acta Crystallogr D Biol Crystallogr, 58, 2170-2172.  
11567612 H.Yu, C.A.Saura, S.Y.Choi, L.D.Sun, X.Yang, M.Handler, T.Kawarabayashi, L.Younkin, B.Fedeles, M.A.Wilson, S.Younkin, E.R.Kandel, A.Kirkwood, and J.Shen (2001).
APP processing and synaptic plasticity in presenilin-1 conditional knockout mice.
  Neuron, 31, 713-726.  
10747019 C.Zwahlen, S.C.Li, L.E.Kay, T.Pawson, and J.D.Forman-Kay (2000).
Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb.
  EMBO J, 19, 1505-1515.
PDB code: 1ddm
10940243 J.H.Hurley, and S.Misra (2000).
Signaling and subcellular targeting by membrane-binding domains.
  Annu Rev Biophys Biomol Struct, 29, 49-79.  
10970839 K.Hamada, T.Shimizu, T.Matsui, S.Tsukita, and T.Hakoshima (2000).
Structural basis of the membrane-targeting and unmasking mechanisms of the radixin FERM domain.
  EMBO J, 19, 4449-4462.
PDB codes: 1gc6 1gc7
10629055 S.H.Ong, G.R.Guy, Y.R.Hadari, S.Laks, N.Gotoh, J.Schlessinger, and I.Lax (2000).
FRS2 proteins recruit intracellular signaling pathways by binding to diverse targets on fibroblast growth factor and nerve growth factor receptors.
  Mol Cell Biol, 20, 979-989.  
10704223 T.A.Ramelot, L.N.Gentile, and L.K.Nicholson (2000).
Transient structure of the amyloid precursor protein cytoplasmic tail indicates preordering of structure for binding to cytosolic factors.
  Biochemistry, 39, 2714-2725.  
10610414 B.Margolis, J.P.Borg, S.Straight, and D.Meyer (1999).
The function of PTB domain proteins.
  Kidney Int, 56, 1230-1237.  
10461172 B.Margolis (1999).
The PTB Domain: The Name Doesn't Say It All.
  Trends Endocrinol Metab, 10, 262-267.  
  10373567 B.W.Howell, L.M.Lanier, R.Frank, F.B.Gertler, and J.A.Cooper (1999).
The disabled 1 phosphotyrosine-binding domain binds to the internalization signals of transmembrane glycoproteins and to phospholipids.
  Mol Cell Biol, 19, 5179-5188.  
10336668 D.M.McLoughlin, N.G.Irving, J.Brownlees, J.P.Brion, K.Leroy, and C.C.Miller (1999).
Mint2/X11-like colocalizes with the Alzheimer's disease amyloid precursor protein and is associated with neuritic plaques in Alzheimer's disease.
  Eur J Neurosci, 11, 1988-1994.  
10549287 F.Poy, M.B.Yaffe, J.Sayos, K.Saxena, M.Morra, J.Sumegi, L.C.Cantley, C.Terhorst, and M.J.Eck (1999).
Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition.
  Mol Cell, 4, 555-561.
PDB codes: 1d1z 1d4t 1d4w
10607674 J.D.Forman-Kay, and T.Pawson (1999).
Diversity in protein recognition by PTB domains.
  Curr Opin Struct Biol, 9, 690-695.  
10338211 K.E.Prehoda, D.J.Lee, and W.A.Lim (1999).
Structure of the enabled/VASP homology 1 domain-peptide complex: a key component in the spatial control of actin assembly.
  Cell, 97, 471-480.
PDB code: 1evh
10542412 N.Blomberg, E.Baraldi, M.Nilges, and M.Saraste (1999).
The PH superfold: a structural scaffold for multiple functions.
  Trends Biochem Sci, 24, 441-445.  
10607564 S.C.Li, G.Gish, D.Yang, A.J.Coffey, J.D.Forman-Kay, I.Ernberg, L.E.Kay, and T.Pawson (1999).
Novel mode of ligand binding by the SH2 domain of the human XLP disease gene product SAP/SH2D1A.
  Curr Biol, 9, 1355-1362.  
10411883 S.Dhe-Paganon, E.A.Ottinger, R.T.Nolte, M.J.Eck, and S.E.Shoelson (1999).
Crystal structure of the pleckstrin homology-phosphotyrosine binding (PH-PTB) targeting region of insulin receptor substrate 1.
  Proc Natl Acad Sci U S A, 96, 8378-8383.
PDB code: 1qqg
10551880 S.E.Dho, M.B.French, S.A.Woods, and C.J.McGlade (1999).
Characterization of four mammalian numb protein isoforms. Identification of cytoplasmic and membrane-associated variants of the phosphotyrosine binding domain.
  J Biol Chem, 274, 33097-33104.  
9890987 S.Tomita, T.Ozaki, H.Taru, S.Oguchi, S.Takeda, Y.Yagi, S.Sakiyama, Y.Kirino, and T.Suzuki (1999).
Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein.
  J Biol Chem, 274, 2243-2254.  
9822620 J.P.Borg, S.W.Straight, S.M.Kaech, Taddéo-Borg, D.E.Kroon, D.Karnak, R.S.Turner, S.K.Kim, and B.Margolis (1998).
Identification of an evolutionarily conserved heterotrimeric protein complex involved in protein targeting.
  J Biol Chem, 273, 31633-31636.  
9614075 J.P.Borg, Y.Yang, M.De Taddéo-Borg, B.Margolis, and R.S.Turner (1998).
The X11alpha protein slows cellular amyloid precursor protein processing and reduces Abeta40 and Abeta42 secretion.
  J Biol Chem, 273, 14761-14766.  
9838094 M.J.Bottomley, K.Salim, and G.Panayotou (1998).
Phospholipid-binding protein domains.
  Biochim Biophys Acta, 1436, 165-183.  
9712855 M.Sastre, R.S.Turner, and E.Levy (1998).
X11 interaction with beta-amyloid precursor protein modulates its cellular stabilization and reduces amyloid beta-protein secretion.
  J Biol Chem, 273, 22351-22357.  
9660863 R.G.Kibbey, J.Rizo, L.M.Gierasch, and R.G.Anderson (1998).
The LDL receptor clustering motif interacts with the clathrin terminal domain in a reverse turn conformation.
  J Cell Biol, 142, 59-67.  
9753324 S.Butz, M.Okamoto, and T.C.Südhof (1998).
A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain.
  Cell, 94, 773-782.  
9846878 S.C.Li, C.Zwahlen, S.J.Vincent, C.J.McGlade, L.E.Kay, T.Pawson, and J.D.Forman-Kay (1998).
Structure of a Numb PTB domain-peptide complex suggests a basis for diverse binding specificity.
  Nat Struct Biol, 5, 1075-1083.
PDB code: 2nmb
9535908 S.E.Dho, S.Jacob, C.D.Wolting, M.B.French, L.R.Rohrschneider, and C.J.McGlade (1998).
The mammalian numb phosphotyrosine-binding domain. Characterization of binding specificity and identification of a novel PDZ domain-containing numb binding protein, LNX.
  J Biol Chem, 273, 9179-9187.  
9434904 D.Cowburn (1997).
Peptide recognition by PTB and PDZ domains.
  Curr Opin Struct Biol, 7, 835-838.  
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.