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PDBsum entry 1fho

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protein links
Signaling protein PDB id
1fho
Jmol PyMol
Contents
Protein chain
119 a.a.
PDB id:
1fho
Name: Signaling protein
Title: Solution structure of the ph domain from thE C. Elegans muscle protein unc-89
Structure: Unc-89. Chain: a. Fragment: pleckstrin homology (ph) domain. Engineered: yes
Source: Caenorhabditis elegans. Organism_taxid: 6239. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 25 models
Authors: N.Blomberg,E.Baraldi,M.Sattler,M.Saraste,M.Nilges
Key ref:
N.Blomberg et al. (2000). Structure of a PH domain from the C. elegans muscle protein UNC-89 suggests a novel function. Structure, 8, 1079-1087. PubMed id: 11080629 DOI: 10.1016/S0969-2126(00)00509-8
Date:
02-Aug-00     Release date:   04-Oct-00    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
O01761  (UNC89_CAEEL) -  Muscle M-line assembly protein unc-89
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8081 a.a.
119 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
DOI no: 10.1016/S0969-2126(00)00509-8 Structure 8:1079-1087 (2000)
PubMed id: 11080629  
 
 
Structure of a PH domain from the C. elegans muscle protein UNC-89 suggests a novel function.
N.Blomberg, E.Baraldi, M.Sattler, M.Saraste, M.Nilges.
 
  ABSTRACT  
 
BACKGROUND: Pleckstrin homology (PH) domains constitute a structurally conserved family present in many signaling and regulatory proteins. PH domains have been shown to bind to phospholipids, and many function in membrane targeting. They generally have a strong electrostatic polarization and interact with negatively charged phospholipids via the positive pole. On the basis of electrostatic modeling, however, we have previously identified a class of PH domains with a predominantly negative charge and predicted that these domains recognize other targets. Here, we report the first experimental structure of such a PH domain. RESULTS: The structure of the PH domain from Caenorhabditis elegans muscle protein UNC-89 has been determined by heteronuclear NMR. The domain adopts the classic PH fold, but has an unusual closed conformation of the "inositol binding loops. This creates a small opening to a deep hydrophobic pocket lined with negative charges on one side, and provides a molecular explanation for the lack of association with inositol-1,4,5-triphosphate. As predicted, the PH domain of UNC-89 has a strongly negative overall electrostatic potential. Modeling the Dbl homology (DH)-linked PH domains from the C. elegans genome shows that a large proportion of these modules are negatively charged. CONCLUSIONS: We present the first structure of a PH domain with a strong negative overall electrostatic potential. The presence of a deep pocket lined with negative charges suggests that the domain binds to ligands other than acidic phospholipids. The abundance of this class of PH domain in the C. elegans genome suggests a prominent role in mediating protein-protein interactions.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Charged Surface around Hydrophobic PocketCharged surface of the UNC-89 PH domain in the same orientation as in Figure 4 and (b) turned 90 so as to view the pocket between the b1-b2 and b3-b4 loop. Blue regions correspond to a positive surface potential, red to a negative. The arrow points into the opening of the hydrophobic pocket

 
  The above figure is reprinted by permission from Cell Press: Structure (2000, 8, 1079-1087) copyright 2000.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  19789381 A.Kontrogianni-Konstantopoulos, M.A.Ackermann, A.L.Bowman, S.V.Yap, and R.J.Bloch (2009).
Muscle giants: molecular scaffolds in sarcomerogenesis.
  Physiol Rev, 89, 1217-1267.  
17534883 A.A.Shahkhatuni, A.G.Shahkhatuni, H.A.Panosyan, A.B.Sahakyan, I.J.Byeon, and A.M.Gronenborn (2007).
Assessment of solvent effects: do weak alignment media affect the structure of the solute?
  Magn Reson Chem, 45, 557-563.  
16453163 T.M.Ferrara, D.B.Flaherty, and G.M.Benian (2005).
Titin/connectin-related proteins in C. elegans: a review and new findings.
  J Muscle Res Cell Motil, 26, 435-447.  
12885767 G.E.Cozier, D.Bouyoucef, and P.J.Cullen (2003).
Engineering the phosphoinositide-binding profile of a class I pleckstrin homology domain.
  J Biol Chem, 278, 39489-39496.  
12930993 S.M.Singh, and D.Murray (2003).
Molecular modeling of the membrane targeting of phospholipase C pleckstrin homology domains.
  Protein Sci, 12, 1934-1953.  
12972602 T.J.Kubiseski, J.Culotti, and T.Pawson (2003).
Functional analysis of the Caenorhabditis elegans UNC-73B PH domain demonstrates a role in activation of the Rac GTPase in vitro and axon guidance in vivo.
  Mol Cell Biol, 23, 6823-6835.  
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.

 

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