title: The interaction properties of the human Rab GTPase family--comparative analysis reveals determinants of molecular binding selectivity.
abstract: BACKGROUND
  Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood.
  
  
  RESULTS
  Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics.
  
  
  CONCLUSIONS
  We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity.
authors.affiliation: Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), Heidelberg, Germany. matthias.stein@mpi-magdeburg.mpg.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Stein
authors.forename: Manohar
authors.initials: M
authors.lastname: Pilli
authors.forename: Sabine
authors.initials: S
authors.lastname: Bernauer
authors.forename: Bianca H
authors.initials: BH
authors.lastname: Habermann
authors.forename: Marino
authors.initials: M
authors.lastname: Zerial
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Wade
mesh_terms: D000595:Amino Acid Sequence; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D016415:Sequence Alignment; D055672:Static Electricity; D020691:rab GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D020691:rab GTP-Binding Proteins