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PDBsum entry 2jph

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protein links
Signaling protein, protein binding PDB id
2jph
Jmol
Contents
Protein chain
122 a.a. *
* Residue conservation analysis
PDB id:
2jph
Name: Signaling protein, protein binding
Title: Nmr solution structure of the rho gtpase binding domain of human plexin-b1
Structure: Plexin-b1. Chain: a. Fragment: sequence database residues 1743-1862. Synonym: semaphorin receptor sep. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: plxnb1, kiaa0407, sep. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: Y.Tong,M.Buck
Key ref:
Y.Tong et al. (2008). Insights into oncogenic mutations of plexin-B1 based on the solution structure of the Rho GTPase binding domain. Structure, 16, 246-258. PubMed id: 18275816 DOI: 10.1016/j.str.2007.12.012
Date:
11-May-07     Release date:   18-Mar-08    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
O43157  (PLXB1_HUMAN) -  Plexin-B1
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2135 a.a.
122 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 

 
DOI no: 10.1016/j.str.2007.12.012 Structure 16:246-258 (2008)
PubMed id: 18275816  
 
 
Insights into oncogenic mutations of plexin-B1 based on the solution structure of the Rho GTPase binding domain.
Y.Tong, P.K.Hota, M.B.Hamaneh, M.Buck.
 
  ABSTRACT  
 
The plexin family of transmembrane receptors are important for axon guidance, angiogenesis, but also in cancer. Recently, plexin-B1 somatic missense mutations were found in both primary tumors and metastases of breast and prostate cancers, with several mutations mapping to the Rho GTPase binding domain (RBD) in the cytoplasmic region of the receptor. Here we present the NMR solution structure of this domain, confirming that the protein has both a ubiquitin-like fold and surface features. Oncogenic mutations T1795A and T1802A are located in a loop region, perturb the average structure locally, and have no effect on Rho GTPase binding affinity. Mutations L1815F and L1815P are located at the Rho GTPase binding site and are associated with a complete loss of binding for Rac1 and Rnd1. Both are found to disturb the conformation of the beta3-beta4 sheet and the orientation of surrounding side chains. Our study suggests that the oncogenic behavior of the mutants can be rationalized with reference to the structure of the RBD of plexin-B1.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Location of the Oncogenic Mutations and the Rho GTPase Binding Region
Mutation sites are shown with side chains as ball-and-stick relative to the Rho GTPase binding interface as determined by NMR (Tong et al., 2007). Two plexin Rho GTPase association motifs (PRAMs), residues 1805–1817 and 1834–1841, colored green, are brought together by the tertiary fold.
Figure 9.
Figure 9. Conformational Changes in L1815F and L1815P Mutants
(A) Two regions of interest are shown, with the positions of certain side-chains superimposed on the main chain conformation. (B) Binding site for Rho GTPases viewed from a different angle (as seen from the back of the structure in [A]). Snap-shots of the structure of models after 5 ns of MD at 300K. Region around residue 1815: (C) wild type; (D) L1815F; (E) L1815P.
 
  The above figures are reprinted from an Open Access publication published by Cell Press: Structure (2008, 16, 246-258) copyright 2008.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20858260 E.S.Ch'ng, and A.Kumanogoh (2010).
Roles of Sema4D and Plexin-B1 in tumor progression.
  Mol Cancer, 9, 251.  
20665475 M.Bueno, N.A.Temiz, and C.J.Camacho (2010).
Novel modulation factor quantifies the role of water molecules in protein interactions.
  Proteins, 78, 3226-3234.  
20213668 R.J.Falconer, A.Penkova, I.Jelesarov, and B.M.Collins (2010).
Survey of the year 2008: applications of isothermal titration calorimetry.
  J Mol Recognit, 23, 395-413.  
19717441 H.He, T.Yang, J.R.Terman, and X.Zhang (2009).
Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration.
  Proc Natl Acad Sci U S A, 106, 15610-15615.
PDB code: 3ig3
19843518 Y.Tong, P.K.Hota, J.Y.Penachioni, M.B.Hamaneh, S.Kim, R.S.Alviani, L.Shen, H.He, W.Tempel, L.Tamagnone, H.W.Park, and M.Buck (2009).
Structure and function of the intracellular region of the plexin-b1 transmembrane receptor.
  J Biol Chem, 284, 35962-35972.
PDB code: 3hm6
18660749 M.Franco, and L.Tamagnone (2008).
Tyrosine phosphorylation in semaphorin signalling: shifting into overdrive.
  EMBO Rep, 9, 865-871.  
18321527 S.Bouguet-Bonnet, and M.Buck (2008).
Compensatory and long-range changes in picosecond-nanosecond main-chain dynamics upon complex formation: 15N relaxation analysis of the free and bound states of the ubiquitin-like domain of human plexin-B1 and the small GTPase Rac1.
  J Mol Biol, 377, 1474-1487.  
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.