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PDBsum entry 2iv8

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protein ligands Protein-protein interface(s) links
Endocytosis/regulator PDB id
2iv8
Jmol
Contents
Protein chains
233 a.a. *
14 a.a. *
Ligands
ILE-VAL-PHE
Waters ×16
* Residue conservation analysis
PDB id:
2iv8
Name: Endocytosis/regulator
Title: Beta appendage in complex with b-arrestin peptide
Structure: Ap-2 complex subunit beta-1. Chain: a. Fragment: residues 700-937. Synonym: beta2-appendage, adapter-related protein complex 2 subunit, beta-adaptin, plasma membrane adaptor ha2/ap2 ada beta subunit, clathrin assembly protein complex 2 beta lar chain, ap105b. Engineered: yes. Beta-arrestin-1.
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: brain. Expressed in: eschericia coli. Expression_system_taxid: 511693. Expression_system_variant: plyss. Synthetic: yes. Organism_taxid: 9606
Resolution:
2.80Å     R-factor:   0.220     R-free:   0.369
Authors: M.G.J.Ford,E.M.Schmid,H.T.Mcmahon
Key ref:
E.M.Schmid et al. (2006). Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly. PLoS Biol, 4, 0. PubMed id: 16903783 DOI: 10.1371/journal.pbio.0040262
Date:
08-Jun-06     Release date:   12-Jun-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P63010  (AP2B1_HUMAN) -  AP-2 complex subunit beta
Seq:
Struc:
 
Seq:
Struc:
937 a.a.
233 a.a.
Protein chain
Pfam   ArchSchema ?
P49407  (ARRB1_HUMAN) -  Beta-arrestin-1
Seq:
Struc:
418 a.a.
14 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane coat   2 terms 
  Biological process     vesicle-mediated transport   2 terms 

 

 
DOI no: 10.1371/journal.pbio.0040262 PLoS Biol 4:0 (2006)
PubMed id: 16903783  
 
 
Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly.
E.M.Schmid, M.G.Ford, A.Burtey, G.J.Praefcke, S.Y.Peak-Chew, I.G.Mills, A.Benmerah, H.T.McMahon.
 
  ABSTRACT  
 
Adaptor protein complex 2 alpha and beta-appendage domains act as hubs for the assembly of accessory protein networks involved in clathrin-coated vesicle formation. We identify a large repertoire of beta-appendage interactors by mass spectrometry. These interact with two distinct ligand interaction sites on the beta-appendage (the "top" and "side" sites) that bind motifs distinct from those previously identified on the alpha-appendage. We solved the structure of the beta-appendage with a peptide from the accessory protein Eps15 bound to the side site and with a peptide from the accessory cargo adaptor beta-arrestin bound to the top site. We show that accessory proteins can bind simultaneously to multiple appendages, allowing these to cooperate in enhancing ligand avidities that appear to be irreversible in vitro. We now propose that clathrin, which interacts with the beta-appendage, achieves ligand displacement in vivo by self-polymerisation as the coated pit matures. This changes the interaction environment from liquid-phase, affinity-driven interactions, to interactions driven by solid-phase stability ("matricity"). Accessory proteins that interact solely with the appendages are thereby displaced to areas of the coated pit where clathrin has not yet polymerised. However, proteins such as beta-arrestin (non-visual arrestin) and autosomal recessive hypercholesterolemia protein, which have direct clathrin interactions, will remain in the coated pits with their interacting receptors.
 
  Selected figure(s)  
 
Figure 4.
Figure 4.Eps15 Peptide Binds in a Tight Turn to the Side Site of the β2-Appendage
(A) Ribbon diagram showing peptide in yellow bound to side site of the β-appendage.
(B and C) The two principle Phe residues of the peptide bind in a groove. A single turn of a helix can also be seen for this peptide.
(D) Peptide displayed as a linear chain showing hydrogen-bonding potential (green lines) and hydrophobic interactions (grey lines). A cluster of hydrogen-bonds in the peptide is consistent with the α-helical conformation in this region.
(E) Density map for the peptide contoured at 1.24 σ.
Figure 7.
Figure 7.Selection of Partners to Remain during Coated Pit Maturation; β-Arrestin but not Eps15 Co-Localise with AP2 Adaptors in CCPs
(A) GFP-βarrestin2 C-terminal domain co-localisation with AP2 adaptors while mutants are cytoplasmic. GFP-Eps15-MD is cytoplasmic.
(B) Full length GFP-β-arrestin2 co-localisation with AP2 adaptor following stimulation of GPCR receptors with TRH for 15s. A mutant of β2-appendage interaction does not localise to coated pits.
 
  The above figures are reprinted from an Open Access publication published by Public Library of Science: PLoS Biol (2006, 4, 0-0) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
22552146 C.J.Merrifield (2012).
Fishing for clathrin-coated pit nucleators.
  Nat Cell Biol, 14, 452-454.  
22484487 P.K.Umasankar, S.Sanker, J.R.Thieman, S.Chakraborty, B.Wendland, M.Tsang, and L.M.Traub (2012).
Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning.
  Nat Cell Biol, 14, 488-501.  
20643221 C.G.Angers, and A.J.Merz (2011).
New links between vesicle coats and Rab-mediated vesicle targeting.
  Semin Cell Dev Biol, 22, 18-26.  
21070595 G.Michaux, C.E.Dyer, T.D.Nightingale, E.Gallaud, S.Nurrish, and D.F.Cutler (2011).
A role for Rab10 in von Willebrand factor release discovered by an AP-1 interactor screen in C. elegans.
  J Thromb Haemost, 9, 392-401.  
21779028 H.T.McMahon, and E.Boucrot (2011).
Molecular mechanism and physiological functions of clathrin-mediated endocytosis.
  Nat Rev Mol Cell Biol, 12, 517-533.  
21499258 M.Bai, H.Gad, G.Turacchio, E.Cocucci, J.S.Yang, J.Li, G.V.Beznoussenko, Z.Nie, R.Luo, L.Fu, J.F.Collawn, T.Kirchhausen, A.Luini, and V.W.Hsu (2011).
ARFGAP1 promotes AP-2-dependent endocytosis.
  Nat Cell Biol, 13, 559-567.  
20154091 A.L.Marat, and P.S.McPherson (2010).
The connecdenn family, Rab35 guanine nucleotide exchange factors interfacing with the clathrin machinery.
  J Biol Chem, 285, 10627-10637.  
20160082 A.Pechstein, J.Bacetic, A.Vahedi-Faridi, K.Gromova, A.Sundborger, N.Tomlin, G.Krainer, O.Vorontsova, J.G.Schäfer, S.G.Owe, M.A.Cousin, W.Saenger, O.Shupliakov, and V.Haucke (2010).
Regulation of synaptic vesicle recycling by complex formation between intersectin 1 and the clathrin adaptor complex AP2.
  Proc Natl Acad Sci U S A, 107, 4206-4211.
PDB codes: 3hs8 3hs9
20482656 C.Tamborindeguy, B.Monsion, V.Brault, L.Hunnicutt, H.J.Ju, A.Nakabachi, and E.Van Fleet (2010).
A genomic analysis of transcytosis in the pea aphid, Acyrthosiphon pisum, a mechanism involved in virus transmission.
  Insect Mol Biol, 19, 259-272.  
  20122152 F.Ang, A.P.Wong, M.M.Ng, and J.J.Chu (2010).
Small interference RNA profiling reveals the essential role of human membrane trafficking genes in mediating the infectious entry of dengue virus.
  Virol J, 7, 24.  
20088845 G.A.Pedersen, S.Chakraborty, A.L.Steinhauser, L.M.Traub, and M.Madsen (2010).
AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2.
  Traffic, 11, 706-720.  
20486136 J.Pizarro-Cerdá, M.Bonazzi, and P.Cossart (2010).
Clathrin-mediated endocytosis: what works for small, also works for big.
  Bioessays, 32, 496-504.  
19903820 N.Kahlfeldt, A.Vahedi-Faridi, S.J.Koo, J.G.Schäfer, G.Krainer, S.Keller, W.Saenger, M.Krauss, and V.Haucke (2010).
Molecular basis for association of PIPKI gamma-p90 with clathrin adaptor AP-2.
  J Biol Chem, 285, 2734-2749.
PDB codes: 3h1z 3h85
20700507 P.Neumann-Staubitz, S.L.Hall, J.Kuo, and A.P.Jackson (2010).
Characterization of a temperature-sensitive vertebrate clathrin heavy chain mutant as a tool to study clathrin-dependent events in vivo.
  PLoS One, 5, e12017.  
19931628 R.Lundmark, and S.R.Carlsson (2010).
Driving membrane curvature in clathrin-dependent and clathrin-independent endocytosis.
  Semin Cell Dev Biol, 21, 363-370.  
20421427 Y.Frosi, S.Anastasi, C.Ballarò, G.Varsano, L.Castellani, E.Maspero, S.Polo, S.Alemà, and O.Segatto (2010).
A two-tiered mechanism of EGFR inhibition by RALT/MIG6 via kinase suppression and receptor degradation.
  J Cell Biol, 189, 557-571.  
19602204 B.M.Wagener, N.A.Marjon, C.M.Revankar, and E.R.Prossnitz (2009).
Adaptor protein-2 interaction with arrestin regulates GPCR recycling and apoptosis.
  Traffic, 10, 1286-1300.  
19741093 C.G.Angers, and A.J.Merz (2009).
HOPS interacts with Apl5 at the vacuole membrane and is required for consumption of AP-3 transport vesicles.
  Mol Biol Cell, 20, 4563-4574.  
19710023 D.S.Kang, R.C.Kern, M.A.Puthenveedu, M.von Zastrow, J.C.Williams, and J.L.Benovic (2009).
Structure of an arrestin2-clathrin complex reveals a novel clathrin binding domain that modulates receptor trafficking.
  J Biol Chem, 284, 29860-29872.
PDB codes: 3gc3 3gd1
19499243 E.I.Christensen, P.J.Verroust, and R.Nielsen (2009).
Receptor-mediated endocytosis in renal proximal tubule.
  Pflugers Arch, 458, 1039-1048.  
19317650 G.J.Doherty, and H.T.McMahon (2009).
Mechanisms of endocytosis.
  Annu Rev Biochem, 78, 857-902.  
19010779 G.Salazar, S.Zlatic, B.Craige, A.A.Peden, J.Pohl, and V.Faundez (2009).
Hermansky-Pudlak Syndrome Protein Complexes Associate with Phosphatidylinositol 4-Kinase Type II {alpha} in Neuronal and Non-neuronal Cells.
  J Biol Chem, 284, 1790-1802.  
19287005 J.R.Thieman, S.K.Mishra, K.Ling, B.Doray, R.A.Anderson, and L.M.Traub (2009).
Clathrin Regulates the Association of PIPKI{gamma}661 with the AP-2 Adaptor {beta}2 Appendage.
  J Biol Chem, 284, 13924-13939.  
19696796 L.M.Traub (2009).
Tickets to ride: selecting cargo for clathrin-regulated internalization.
  Nat Rev Mol Cell Biol, 10, 583-596.  
19209226 M.Sone, A.Uchida, A.Komatsu, E.Suzuki, I.Ibuki, M.Asada, H.Shiwaku, T.Tamura, M.Hoshino, H.Okazawa, and Y.Nabeshima (2009).
Loss of yata, a novel gene regulating the subcellular localization of APPL, induces deterioration of neural tissues and lifespan shortening.
  PLoS ONE, 4, e4466.  
19359243 N.Masuyama, T.Kuronita, R.Tanaka, T.Muto, Y.Hirota, A.Takigawa, H.Fujita, Y.Aso, J.Amano, and Y.Tanaka (2009).
HM1.24 is internalized from lipid rafts by clathrin-mediated endocytosis through interaction with alpha-adaptin.
  J Biol Chem, 284, 15927-15941.  
19240038 N.Rudinskiy, Y.Grishchuk, A.Vaslin, J.Puyal, A.Delacourte, H.Hirling, P.G.Clarke, and R.Luthi-Carter (2009).
Calpain hydrolysis of alpha- and beta2-adaptins decreases clathrin-dependent endocytosis and may promote neurodegeneration.
  J Biol Chem, 284, 12447-12458.  
19183301 Y.Zwang, and Y.Yarden (2009).
Systems biology of growth factor-induced receptor endocytosis.
  Traffic, 10, 349-363.  
18211691 C.J.DeRegis, P.B.Rahl, G.R.Hoffman, R.A.Cerione, and R.N.Collins (2008).
Mutational analysis of betaCOP (Sec26p) identifies an appendage domain critical for function.
  BMC Cell Biol, 9, 3.  
18997784 H.C.Hennies, U.Kornak, H.Zhang, J.Egerer, X.Zhang, W.Seifert, J.Kühnisch, B.Budde, M.Nätebus, F.Brancati, W.R.Wilcox, D.Müller, P.B.Kaplan, A.Rajab, G.Zampino, V.Fodale, B.Dallapiccola, W.Newman, K.Metcalfe, J.Clayton-Smith, M.Tassabehji, B.Steinmann, F.A.Barr, P.Nürnberg, P.Wieacker, and S.Mundlos (2008).
Gerodermia osteodysplastica is caused by mutations in SCYL1BP1, a Rab-6 interacting golgin.
  Nat Genet, 40, 1410-1412.  
18430801 J.Jakobsson, H.Gad, F.Andersson, P.Löw, O.Shupliakov, and L.Brodin (2008).
Role of epsin 1 in synaptic vesicle endocytosis.
  Proc Natl Acad Sci U S A, 105, 6445-6450.  
18762582 J.Kasprowicz, S.Kuenen, K.Miskiewicz, R.L.Habets, L.Smitz, and P.Verstreken (2008).
Inactivation of clathrin heavy chain inhibits synaptic recycling but allows bulk membrane uptake.
  J Cell Biol, 182, 1007-1016.  
18200045 J.Rumpf, B.Simon, N.Jung, T.Maritzen, V.Haucke, M.Sattler, and Y.Groemping (2008).
Structure of the Eps15-stonin2 complex provides a molecular explanation for EH-domain ligand specificity.
  EMBO J, 27, 558-569.
PDB code: 2jxc
18498437 J.Z.Rappoport, and S.M.Simon (2008).
A functional GFP fusion for imaging clathrin-mediated endocytosis.
  Traffic, 9, 1250-1255.  
17986441 L.E.Olesen, M.G.Ford, E.M.Schmid, Y.Vallis, M.M.Babu, P.H.Li, I.G.Mills, H.T.McMahon, and G.J.Praefcke (2008).
Solitary and repetitive binding motifs for the AP2 complex alpha-appendage in amphiphysin and other accessory proteins.
  J Biol Chem, 283, 5099-5109.
PDB code: 2vj0
18819912 M.Chaineau, L.Danglot, V.Proux-Gillardeaux, and T.Galli (2008).
Role of HRB in Clathrin-dependent Endocytosis.
  J Biol Chem, 283, 34365-34373.  
18843039 P.A.Keyel, J.R.Thieman, R.Roth, E.Erkan, E.T.Everett, S.C.Watkins, J.E.Heuser, and L.M.Traub (2008).
The AP-2 adaptor beta2 appendage scaffolds alternate cargo endocytosis.
  Mol Biol Cell, 19, 5309-5326.  
18775314 P.R.Pryor, L.Jackson, S.R.Gray, M.A.Edeling, A.Thompson, C.M.Sanderson, P.R.Evans, D.J.Owen, and J.P.Luzio (2008).
Molecular basis for the sorting of the SNARE VAMP7 into endocytic clathrin-coated vesicles by the ArfGAP Hrb.
  Cell, 134, 817-827.
PDB code: 2vx8
17494077 A.A.Kolokoltsov, D.Deniger, E.H.Fleming, N.J.Roberts, J.M.Karpilow, and R.A.Davey (2007).
Small interfering RNA profiling reveals key role of clathrin-mediated endocytosis and early endosome formation for infection by respiratory syncytial virus.
  J Virol, 81, 7786-7800.  
17547704 A.Benmerah, and C.Lamaze (2007).
Clathrin-coated pits: vive la différence?
  Traffic, 8, 970-982.  
17547696 A.Burtey, E.M.Schmid, M.G.Ford, J.Z.Rappoport, M.G.Scott, S.Marullo, S.M.Simon, H.T.McMahon, and A.Benmerah (2007).
The conserved isoleucine-valine-phenylalanine motif couples activation state and endocytic functions of beta-arrestins.
  Traffic, 8, 914-931.  
17702618 A.Young (2007).
Structural insights into the clathrin coat.
  Semin Cell Dev Biol, 18, 448-458.  
17762867 B.Ritter, A.Y.Denisov, J.Philie, P.D.Allaire, V.Legendre-Guillemin, P.Zylbergold, K.Gehring, and P.S.McPherson (2007).
The NECAP PHear domain increases clathrin accessory protein binding potential.
  EMBO J, 26, 4066-4077.  
17488288 E.Eisenberg, and L.E.Greene (2007).
Multiple roles of auxilin and hsc70 in clathrin-mediated endocytosis.
  Traffic, 8, 640-646.  
17631994 E.J.Ungewickell, and L.Hinrichsen (2007).
Endocytosis: clathrin-mediated membrane budding.
  Curr Opin Cell Biol, 19, 417-425.  
17713526 E.M.Schmid, and H.T.McMahon (2007).
Integrating molecular and network biology to decode endocytosis.
  Nature, 448, 883-888.  
17689276 E.Wessels, and J.C.Simpson (2007).
Impact of live cell imaging on coated vesicle research.
  Semin Cell Dev Biol, 18, 412-423.  
17692542 I.G.Mills (2007).
The interplay between clathrin-coated vesicles and cell signalling.
  Semin Cell Dev Biol, 18, 459-470.  
17547698 N.Jung, and V.Haucke (2007).
Clathrin-mediated endocytosis at synapses.
  Traffic, 8, 1129-1136.  
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.