title: bMERB domains are bivalent Rab8 family effectors evolved by gene duplication.
abstract: In their active GTP-bound form, Rab proteins interact with proteins termed effector molecules. In this study, we have thoroughly characterized a Rab effector domain that is present in proteins of the Mical and EHBP families, both known to act in endosomal trafficking. Within our study, we show that these effectors display a preference for Rab8 family proteins (Rab8, 10, 13 and 15) and that some of the effector domains can bind two Rab proteins via separate binding sites. Structural analysis allowed us to explain the specificity towards Rab8 family members and the presence of two similar Rab binding sites that must have evolved via gene duplication. This study is the first to thoroughly characterize a Rab effector protein that contains two separate Rab binding sites within a single domain, allowing Micals and EHBPs to bind two Rabs simultaneously, thus suggesting previously unknown functions of these effector molecules in endosomal trafficking.
authors.affiliation: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Amrita
authors.initials: A
authors.lastname: Rai
authors.affiliation: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Oprisko
authors.affiliation: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Campos
authors.affiliation: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Yangxue
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Timon
authors.initials: T
authors.lastname: Friese
authors.affiliation: Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technische Universität München, Garching, Germany.
authors.forename: Aymelt
authors.initials: A
authors.lastname: Itzen
authors.affiliation: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Roger S
authors.identifier: 0000-0002-0772-0444
authors.initials: RS
authors.lastname: Goody
authors.affiliation: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Emerich Mihai
authors.initials: EM
authors.lastname: Gazdag
authors.affiliation: Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Matthias P
authors.identifier: 0000-0002-1529-8933
authors.initials: MP
authors.lastname: Müller
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D020440:Gene Duplication; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins; D006899:Mixed Function Oxygenases; D000072417:Protein Domains; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000096985:Calponins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D006899:Mixed Function Oxygenases; D020691:rab GTP-Binding Proteins; C485118:EHBP1 protein, human; C455272:MICAL1 protein, human; D000096985:Calponins; C082377:RAB8A protein, human
keywords: EHBP; Mical; Rab effectors; biochemistry; biophysics; human; structural biology