title: Interface analysis of small GTP binding protein complexes suggests preferred membrane orientations.
abstract: Crystal structures of small GTP binding protein complexes with their effectors and regulators reveal that one particularly flat side of the G domain that contains helix α4 and the C-terminal helix α5 is practically devoid of contacts. Although this observation seems trivial as the main binding targets are the switch I and II regions opposite of this side, the fact that all interacting proteins, even the largest ones, seem to avoid occupying this area (except for Ran, that does not localize to membranes) is very striking. An orientation with this 'flat' side parallel to the membrane was proposed before and would allow simultaneous interaction of the lipidated C-terminus and positive charges in the α4 helix with the membrane while being bound to effector or regulator molecules. Furthermore, this 'flat' side might be involved in regulatory mechanisms: a Ras dimer that is found in different crystal forms interacts exactly at this side. Additional interface analysis of GTPase complexes nicely confirms the effect of different flexibilities of the GTP and GDP forms. Besides Ran proteins, guanine nucleotide exchange factors (GEFs) bury the largest surface areas to provide the binding energy to open up the switch regions for nucleotide exchange.
authors.affiliation: Max Planck Institute of Molecular Physiology, Department of Mechanistic Cell Biology, Otto-Hahn-Str. 11, D-44227 Dortmund.
authors.forename: Ingrid R
authors.initials: IR
authors.lastname: Vetter
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006801:Humans; D011499:Protein Processing, Post-Translational
chemical_list: D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; D006153:Guanosine Diphosphate; D019204:GTP-Binding Proteins
keywords: G domain dimerization; GTPase; buried interface; crystal structures; effector complexes; membrane interaction