title: Comparison of the PTS1- and Rab8b-binding properties of Pex5p and Pex5Rp/TRIP8b.
abstract: Tetratricopeptide (TPR)-domain proteins are involved in various cellular processes. The TPR domain is known to be responsible for interaction with other proteins commonly recognizing sequence motifs at the C-termini. One such TPR-protein, TRIP8b, was originally identified in rat as an interaction partner of Rab8b, and its human orthologue as a protein related to the peroxisomal targeting signal 1 (PTS1) receptor Pex5p (Pex5Rp). Somewhat later, the mouse orthologue was reported to bind the hyperpolarization-activated, cyclic nucleotide-regulated HCN channels, and, very recently, the rat orthologue was shown to interact with latrophilin 1, the calcium-independent receptor of alpha-latrotoxin. Here we employed various methodological approaches to investigate and compare the binding specificities of the human PTS1 receptor Pex5p and the related protein Pex5Rp/TRIP8b towards a subset of targets, including Rab8b and various C-termini resembling PTS1. The results show that the TPR domains of Pex5p and Pex5Rp/TRIP8b have distinct but overlapping substrate specificities. This suggests that selectivity in the recognition of substrates by the TPR domains of Pex5p and Pex5Rp/TRIP8b is a matter of considerable complexity, and that no single determinant appears to be sufficient in unambiguously defining a binding target for either protein. This idea is further corroborated by our observations that changes in the surrounding residues or the conformational state of one of the binding partners can profoundly alter their binding activities. The implications of these findings for the possible peroxisome-related functions of Pex5Rp/TRIP8b are discussed.
authors.affiliation: Katholieke Universiteit Leuven, Campus Gasthuisberg (O&N 1), Departement Moleculaire Celbiologie, LIPIT, Leuven, Belgium. marc.fransen@med.kuleuven.be
authors.forename: Marc
authors.initials: M
authors.lastname: Fransen
authors.forename: Leen
authors.initials: L
authors.lastname: Amery
authors.forename: Andreas
authors.initials: A
authors.lastname: Hartig
authors.forename: Chantal
authors.initials: C
authors.lastname: Brees
authors.forename: Anja
authors.initials: A
authors.lastname: Rabijns
authors.forename: Guy P
authors.initials: GP
authors.lastname: Mannaerts
authors.forename: Paul P
authors.initials: PP
authors.lastname: Van Veldhoven
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D051379:Mice; D008958:Models, Molecular; D015513:Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D011485:Protein Binding; D021382:Protein Sorting Signals; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism; D040681:Structural Homology, Protein; D020691:rab GTP-Binding Proteins
chemical_list: D015513:Oncogene Proteins; C529762:PEX5L protein, human; D000074435:Peroxisome-Targeting Signal 1 Receptor; D021382:Protein Sorting Signals; C529761:Rab8b protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D020691:rab GTP-Binding Proteins