Structural biology of Arf and Rab GTPases' effector recruitment and specificity

Structure. 2013 Aug 6;21(8):1284-97. doi: 10.1016/j.str.2013.06.016.

Abstract

Arf and Rab proteins, members of small GTPases superfamily, localize to specific subcellular compartments and regulate intracellular trafficking. To carry out their cellular functions, Arfs/Rabs interact with numerous and structurally diverse effector proteins. Over the years, a number of Arf/Rab:effector complexes have been crystallized and their structures reveal shared binding modes including α-helical packing, β-β complementation, and heterotetrameric assemblies. We review available structural information and provide a framework for in-depth analysis of complexes. The unifying features that we identify are organized into a classification scheme for different modes of Arf/Rab:effector interactions, which includes "all-α-helical," "mixed α-helical," "β-β zipping," and "bivalent" modes of binding. Additionally, we highlight structural determinants that are the basis of effector specificity. We conclude by expanding on functional implications that are emerging from available structural information under our proposed classification scheme.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADP-Ribosylation Factors / chemistry*
  • Amino Acid Sequence
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • rab GTP-Binding Proteins / chemistry*

Substances

  • ADP-Ribosylation Factors
  • rab GTP-Binding Proteins