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PDBsum entry 1zsh
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protein ligands metals links
Signaling protein PDB id
1zsh

 

 

 

 

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Contents
Protein chain
354 a.a. *
Ligands
IHP
Metals
_MG
Waters ×93
* Residue conservation analysis
PDB id:
1zsh
Name: Signaling protein
Title: Crystal structure of bovine arrestin-2 in complex with inositol hexakisphosphate (ip6)
Structure: Beta-arrestin 1. Chain: a. Synonym: arrestin, beta 1. Engineered: yes
Source: Bos taurus. Cattle. Organism_taxid: 9913. Gene: arrb1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.90Å     R-factor:   0.250     R-free:   0.260
Authors: S.K.Milano,Y.M.Kim,F.P.Stefano,J.L.Benovic,C.Brenner
Key ref:
S.K.Milano et al. (2006). Nonvisual arrestin oligomerization and cellular localization are regulated by inositol hexakisphosphate binding. J Biol Chem, 281, 9812-9823. PubMed id: 16439357 DOI: 10.1074/jbc.M512703200
Date:
24-May-05     Release date:   31-Jan-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
P17870  (ARRB1_BOVIN) -  Beta-arrestin-1 from Bos taurus
Seq:
Struc: 		418 a.a.
354 a.a.
Key:    Secondary structure  CATH domain

 

 
DOI no: 10.1074/jbc.M512703200 J Biol Chem 281:9812-9823 (2006)
PubMed id: 16439357  
 
 
Nonvisual arrestin oligomerization and cellular localization are regulated by inositol hexakisphosphate binding.
S.K.Milano, Y.M.Kim, F.P.Stefano, J.L.Benovic, C.Brenner.
 
  ABSTRACT  
 
Interactions between arrestins and phosphoinositides have been reported to regulate multiple membrane-associated signaling and trafficking events including clathrin-mediated endocytosis and light adaptation in Drosophila. Arrestins have been proposed to have nuclear and cytosolic functions as well, although the ligand dependence of these functions has not been investigated. Here we characterize the structural, molecular, and cellular interactions between arrestin-2 and inositol hexakisphosphate (inositol 1,2,3,4,5,6-hexakisphosphate (IP(6))). The crystal structure of the arrestin-2.IP(6) complex was solved to 2.9 A with crystal lattice contacts suggesting two sites on a protein monomer mediating IP(6) binding. Mutagenesis coupled to isothermal titration calorimetry and tritiated IP(6) binding assays confirmed two-site binding with a low affinity IP(6)-binding site in the N-domain and a high affinity site in the C-domain. Native gel electrophoresis, gel filtration, and analytical ultracentrifugation demonstrated the ability of IP(6) to promote arrestin-2 oligomerization via the two crystallographically defined ligand-binding locations. In addition, analysis in mammalian cells revealed that arrestin-2 not only undergoes homo-oligomerization, but it can also hetero-oligomerize with arrestin-3 in a manner that depends on IP(6)-binding sites. Mutation of either IP(6)-binding site in arrestin-2 disrupted oligomerization while interactions with known binding partners including clathrin, AP-2, and ERK2 were maintained. Subcellular localization studies showed that arrestin-2 oligomers are primarily cytoplasmic, whereas arrestin-2 monomers displayed increased nuclear localization. Thus, by promoting cytosolic oligomerization, IP(6) binding is proposed to be a negative regulator of interactions of arrestin with plasma membrane and nuclear signaling proteins.
 
  Selected figure(s)  
 
Figure 5.
Arrestin-2 and -3 can homo- and heteroassociate in COS-1 cells. A, co-immunoprecipitation experiment showing wild type arrestin-2 associating with itself. Mutation of the two crystallographically defined IP[6]-binding sites on arrestin-2, either independently or combined, disrupts self-association. HA-tagged wild type and mutant arrestin-2 proteins were overexpressed in COS-1 cells with or without FLAG-tagged wild type arrestin-2. HA-arrestins were immunoprecipitated and blotted for FLAG-arrestin-2. Immunoprecipitate (IP) and lysate expression levels are shown. B and C, co-immunoprecipitation experiments showing arrestin-2 mutants effectively interacting with known binding partners. HA-tagged wild type and mutant arrestin-2 proteins were overexpressed in COS-1 cells. HA-arrestins were immunoprecipitated and blotted for clathrin, β[2]-adaptin, and ERK2. Immunoprecipitate and lysate expression levels are shown. D, co-immunoprecipitation experiment showing that wild type arrestin-2 and -3 can homo- and heteroassociate. HA-tagged arrestin-2 and -3 proteins were overexpressed in COS-1 cells with or without FLAG-tagged arrestin-2 or -3. HA-arrestins were immunoprecipitated and blotted for FLAG-arrestins. -indicates mock transfection. IB, immunoblot; WT, wild type; arr2, arrestin-2; arr3, arrestin-3. 		Figure 6.
Arrestin-2 oligomers are deficient in nuclear transport. HEK293 cells were transiently transfected with either wild type (WT) or mutant arrestin-2 proteins. 48 h post-transfection the cells were fixed and stained with 4′,6-diamidino-2-phenylindole (DAPI). The slides were visualized, and images were acquired on an Olympus BX-61 fluorescence microscope.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 9812-9823) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21380751 E.Png, W.Lan, M.Lazaroo, S.Chen, L.Zhou, and L.Tong (2011).
A new method of high-speed cellular protein separation and insight into subcellular compartmentalization of proteins.
  Anal Bioanal Chem, 400, 767-775.  
21086182 X.Feng, W.Wang, J.Liu, and Y.Liu (2011).
β-Arrestins: multifunctional signaling adaptors in type 2 diabetes.
  Mol Biol Rep, 38, 2517-2528.  
20980661 B.Sarmah, and S.R.Wente (2010).
Inositol hexakisphosphate kinase-2 acts as an effector of the vertebrate Hedgehog pathway.
  Proc Natl Acad Sci U S A, 107, 19921-19926.  
20056609 H.Shankar, A.Michal, R.C.Kern, D.S.Kang, V.V.Gurevich, and J.L.Benovic (2010).
Non-visual arrestins are constitutively associated with the centrosome and regulate centrosome function.
  J Biol Chem, 285, 8316-8329.  
19914276 P.W.Majerus, D.B.Wilson, C.Zhang, P.J.Nicholas, and M.P.Wilson (2010).
Expression of inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) and its role in neural tube defects.
  Adv Enzyme Regul, 50, 365-372.  
20421423 S.Mangmool, A.K.Shukla, and H.A.Rockman (2010).
beta-Arrestin-dependent activation of Ca(2+)/calmodulin kinase II after beta(1)-adrenergic receptor stimulation.
  J Cell Biol, 189, 573-587.  
  20412604 V.V.Gurevich, and E.V.Gurevich (2010).
Custom-designed proteins as novel therapeutic tools? The case of arrestins.
  Expert Rev Mol Med, 12, e13.  
19153083 D.Meng, M.J.Lynch, E.Huston, M.Beyermann, J.Eichhorst, D.R.Adams, E.Klussmann, E.Klusmann, M.D.Houslay, and G.S.Baillie (2009).
MEK1 binds directly to betaarrestin1, influencing both its phosphorylation by ERK and the timing of its isoprenaline-stimulated internalization.
  J Biol Chem, 284, 11425-11435.  
19794886 L.Aubry, D.Guetta, and G.Klein (2009).
The arrestin fold: variations on a theme.
  Curr Genomics, 10, 133-142.  
19176359 L.Rojanathammanee, E.B.Harmon, L.A.Grisanti, P.Govitrapong, M.Ebadi, B.D.Grove, M.Miyagi, and J.E.Porter (2009).
The 27-kDa heat shock protein confers cytoprotective effects through a beta 2-adrenergic receptor agonist-initiated complex with beta-arrestin.
  Mol Pharmacol, 75, 855-865.  
19482943 M.P.Wilson, C.Hugge, M.Bielinska, P.Nicholas, P.W.Majerus, and D.B.Wilson (2009).
Neural tube defects in mice with reduced levels of inositol 1,3,4-trisphosphate 5/6-kinase.
  Proc Natl Acad Sci U S A, 106, 9831-9835.  
19001375 X.Song, S.Coffa, H.Fu, and V.V.Gurevich (2009).
How does arrestin assemble MAPKs into a signaling complex?
  J Biol Chem, 284, 685-695.  
17943301 A.R.Alcázar-Román, and S.R.Wente (2008).
Inositol polyphosphates: a new frontier for regulating gene expression.
  Chromosoma, 117, 1.  
18088321 B.M.Collins, S.J.Norwood, M.C.Kerr, D.Mahony, M.N.Seaman, R.D.Teasdale, and D.J.Owen (2008).
Structure of Vps26B and Mapping of its Interaction with the Retromer Protein Complex.
  Traffic, 9, 366-379.
PDB code: 2r51
18664266 C.E.Alvarez (2008).
On the origins of arrestin and rhodopsin.
  BMC Evol Biol, 8, 222.  
17965750 G.Milligan (2008).
A day in the life of a G protein-coupled receptor: the contribution to function of G protein-coupled receptor dimerization.
  Br J Pharmacol, 153, S216-S229.  
18200608 O.Okhrimenko, and I.Jelesarov (2008).
A survey of the year 2006 literature on applications of isothermal titration calorimetry.
  J Mol Recognit, 21, 1.  
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.  
18547524 S.M.Hanson, E.S.Dawson, D.J.Francis, N.Van Eps, C.S.Klug, W.L.Hubbell, J.Meiler, and V.V.Gurevich (2008).
A model for the solution structure of the rod arrestin tetramer.
  Structure, 16, 924-934.  
18161994 S.M.Hanson, S.A.Vishnivetskiy, W.L.Hubbell, and V.V.Gurevich (2008).
Opposing effects of inositol hexakisphosphate on rod arrestin and arrestin2 self-association.
  Biochemistry, 47, 1070-1075.  
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.  
17037978 C.A.Moore, S.K.Milano, and J.L.Benovic (2007).
Regulation of receptor trafficking by GRKs and arrestins.
  Annu Rev Physiol, 69, 451-482.  
17984062 C.Boularan, M.G.Scott, K.Bourougaa, M.Bellal, E.Esteve, A.Thuret, A.Benmerah, M.Tramier, M.Coppey-Moisan, C.Labbé-Jullié, R.Fåhraeus, and S.Marullo (2007).
beta-arrestin 2 oligomerization controls the Mdm2-dependent inhibition of p53.
  Proc Natl Acad Sci U S A, 104, 18061-18066.  
17125841 C.Oro, H.Qian, and W.G.Thomas (2007).
Type 1 angiotensin receptor pharmacology: signaling beyond G proteins.
  Pharmacol Ther, 113, 210-226.  
17620599 K.Xiao, D.B.McClatchy, A.K.Shukla, Y.Zhao, M.Chen, S.K.Shenoy, J.R.Yates, and R.J.Lefkowitz (2007).
Functional specialization of beta-arrestin interactions revealed by proteomic analysis.
  Proc Natl Acad Sci U S A, 104, 12011-12016.  
17666399 S.K.Shenoy, L.S.Barak, K.Xiao, S.Ahn, M.Berthouze, A.K.Shukla, L.M.Luttrell, and R.J.Lefkowitz (2007).
Ubiquitination of beta-arrestin links seven-transmembrane receptor endocytosis and ERK activation.
  J Biol Chem, 282, 29549-29562.  
17305471 S.M.DeWire, S.Ahn, R.J.Lefkowitz, and S.K.Shenoy (2007).
Beta-arrestins and cell signaling.
  Annu Rev Physiol, 69, 483-510.  
16903783 E.M.Schmid, M.G.Ford, A.Burtey, G.J.Praefcke, S.Y.Peak-Chew, I.G.Mills, A.Benmerah, and H.T.McMahon (2006).
Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly.
  PLoS Biol, 4, e262.
PDB codes: 2iv8 2iv9
17020596 E.V.Gurevich, and V.V.Gurevich (2006).
Arrestins: ubiquitous regulators of cellular signaling pathways.
  Genome Biol, 7, 236.  
16806884 T.J.Brett, and L.M.Traub (2006).
Molecular structures of coat and coat-associated proteins: function follows form.
  Curr Opin Cell Biol, 18, 395-406.  
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.

 

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