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PDBsum entry 2adz

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Protein binding PDB id
2adz
Jmol
Contents
Protein chain
178 a.a. *
* Residue conservation analysis
PDB id:
2adz
Name: Protein binding
Title: Solution structure of the joined ph domain of alpha1- syntrophin
Structure: Alpha-1-syntrophin. Chain: a. Fragment: ph domain. Synonym: alpha-syntrophin. Engineered: yes
Source: Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: J.Yan,W.Wen,W.Xu,J.F.Long,M.E.Adams,S.C.Froehner,M.Zhang
Key ref:
J.Yan et al. (2005). Structure of the split PH domain and distinct lipid-binding properties of the PH-PDZ supramodule of alpha-syntrophin. EMBO J, 24, 3985-3995. PubMed id: 16252003 DOI: 10.1038/sj.emboj.7600858
Date:
21-Jul-05     Release date:   24-Jan-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q61234  (SNTA1_MOUSE) -  Alpha-1-syntrophin
Seq:
Struc:
503 a.a.
178 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 

 
DOI no: 10.1038/sj.emboj.7600858 EMBO J 24:3985-3995 (2005)
PubMed id: 16252003  
 
 
Structure of the split PH domain and distinct lipid-binding properties of the PH-PDZ supramodule of alpha-syntrophin.
J.Yan, W.Wen, W.Xu, J.F.Long, M.E.Adams, S.C.Froehner, M.Zhang.
 
  ABSTRACT  
 
Pleckstrin homology (PH) domains play diverse roles in cytoskeletal dynamics and signal transduction. Split PH domains represent a unique subclass of PH domains that have been implicated in interactions with complementary partial PH domains 'hidden' in many proteins. Whether partial PH domains exist as independent structural units alone and whether two halves of a split PH domain can fold together to form an intact PH domain are not known. Here, we solved the structure of the PH(N)-PDZ-PH(C) tandem of alpha-syntrophin. The split PH domain of alpha-syntrophin adopts a canonical PH domain fold. The isolated partial PH domains of alpha-syntrophin, although completely unfolded, remain soluble in solution. Mixing of the two isolated domains induces de novo folding and yields a stable PH domain. Our results demonstrate that two complementary partial PH domains are capable of binding to each other to form an intact PH domain. We further showed that the PH(N)-PDZ-PH(C) tandem forms a functionally distinct supramodule, in which the split PH domain and the PDZ domain function synergistically in binding to inositol phospholipids.
 
  Selected figure(s)  
 
Figure 3.
Figure 3 Folding and interaction of the two isolated, partial PH domain fragments. (A) SDS-PAGE showing the purification of the joined PH[N]-'C'-PH[C] domain and cleavage of the domain into PH[N] and PH[C] fragments. (B) Overlay plot of the 1H, 15N HSQC spectra of the joined PH[N]-'C'-PH[C] (black) and its protease cleaved form (red). 1H, 15N HSQC spectra of the isolated PH[N] (C) and PH[C] (D) fragments. (E) Overlay plot of the 1H, 15N HSQC spectra of the joined PH[N]-'C'-PH[C] (black) and the 1:1 mixture of the two halves of the split PH domain (red).
Figure 5.
Figure 5 Lipid-binding specificity of the PH[N]-PDZ-PH[C] supramodule using phospholipid strip overlay assay. (A) Binding of the PH[N]-PDZ-PH[C] tandem to the phospholipids spotted on a cellulose membrane. The amount of lipid per spot was 100 pmol. Abbreviations for the lipids: S1P: sphingosine-1-phosphate; LPA: lysophosphatidic acid; LPC: lysophosphocholine; PE: phosphatidylethanolamine; PS: phosphatidylserine; PA: phosphatidic acid; PC: phosphatidylcholine; PtdIns: phosphatidylinositol. The amount of protein used in the assay is 0.5 g/ml. (B) Binding isotherms of PH[N]-PDZ-PH[C] with PC/PS liposomes containing either 10 or 20% PI(3,5)P[2]. (C) Identification of the residues in the split PH domain of the PH[N]-PDZ-PH[C] tandem that are involved in the lipid binding.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2005, 24, 3985-3995) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20720107 M.E.Adams, K.N.Anderson, and S.C.Froehner (2010).
The alpha-syntrophin PH and PDZ domains scaffold acetylcholine receptors, utrophin, and neuronal nitric oxide synthase at the neuromuscular junction.
  J Neurosci, 30, 11004-11010.  
19961569 S.V.Boehm, P.Constantinou, S.Tan, H.Jin, and R.G.Roberts (2009).
Profound human/mouse differences in alpha-dystrobrevin isoforms: a novel syntrophin-binding site and promoter missing in mouse and rat.
  BMC Biol, 7, 85.  
19153575 W.Feng, and M.Zhang (2009).
Organization and dynamics of PDZ-domain-related supramodules in the postsynaptic density.
  Nat Rev Neurosci, 10, 87-99.  
18618698 Y.Kong, and M.Karplus (2009).
Signaling pathways of PDZ2 domain: a molecular dynamics interaction correlation analysis.
  Proteins, 74, 145-154.  
18728011 C.Walliser, M.Retlich, R.Harris, K.L.Everett, M.B.Josephs, P.Vatter, D.Esposito, P.C.Driscoll, M.Katan, P.Gierschik, and T.D.Bunney (2008).
Rac Regulates Its Effector Phospholipase C{gamma}2 through Interaction with a Split Pleckstrin Homology Domain.
  J Biol Chem, 283, 30351-30362.
PDB code: 2k2j
18496527 T.Krojer, J.Sawa, E.Schäfer, H.R.Saibil, M.Ehrmann, and T.Clausen (2008).
Structural basis for the regulated protease and chaperone function of DegP.
  Nature, 453, 885-890.
PDB codes: 2zle 3cs0
18640982 W.Wen, W.Liu, J.Yan, and M.Zhang (2008).
Structure basis and unconventional lipid membrane binding properties of the PH-C1 tandem of rho kinases.
  J Biol Chem, 283, 26263-26273.  
18082612 H.Wu, W.Feng, J.Chen, L.N.Chan, S.Huang, and M.Zhang (2007).
PDZ domains of Par-3 as potential phosphoinositide signaling integrators.
  Mol Cell, 28, 886-898.
PDB code: 2ogp
17914463 L.Pan, H.Wu, C.Shen, Y.Shi, W.Jin, J.Xia, and M.Zhang (2007).
Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes.
  EMBO J, 26, 4576-4587.
PDB code: 2pku
17057716 S.L.Alam, C.Langelier, F.G.Whitby, S.Koirala, H.Robinson, C.P.Hill, and W.I.Sundquist (2006).
Structural basis for ubiquitin recognition by the human ESCRT-II EAP45 GLUE domain.
  Nat Struct Mol Biol, 13, 1029-1030.
PDB code: 2hth
16500902 W.Wen, J.Yan, and M.Zhang (2006).
Structural characterization of the split pleckstrin homology domain in phospholipase C-gamma1 and its interaction with TRPC3.
  J Biol Chem, 281, 12060-12068.
PDB code: 2fjl
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.