4d0g
Structure of Rab14 in complex with Rab-Coupling Protein (RCP)
Structural highlights
FunctionRAB14_HUMAN Involved in membrane trafficking between the Golgi complex and endosomes during early embryonic development. Regulates the Golgi to endosome transport of FGFR-containing vesicles during early development, a key process for developing basement membrane and epiblast and primitive endoderm lineages during early postimplantation development. May act by modulating the kinesin KIF16B-cargo association to endosomes (By similarity). Regulates, together with its guanine nucleotide exchange factor DENND6A, the specific endocytic transport of ADAM10, N-cadherin/CDH2 shedding and cell-cell adhesion.[1] Publication Abstract from PubMedRab GTPases recruit effector proteins, via their GTP-dependent switch regions, to distinct sub-cellular compartments. Rab11 and Rab25 are closely related small GTPases that bind to common effectors termed the Rab11-Family of Interacting Proteins (FIPs). The FIPs are organized into two subclasses (class I and class II) based on sequence and domain organization, and both subclasses contain a highly conserved Rab-binding domain (RBD) at their C-termini. Yeast two-hybrid and biochemical studies have revealed that the more distantly related Rab14 also interacts with class I FIPs. Here, we perform detailed structural, thermodynamic and cellular analyses of the interactions between Rab14 and one of the class I FIPs - the Rab Coupling Protein (RCP) - to clarify the molecular aspects of the interaction. We find that Rab14 indeed binds to RCP, albeit with reduced affinity relative to conventional Rab11:FIP and Rab25:FIP complexes. However, in vivo, Rab11 recruits RCP onto biological membranes. Furthermore, biophysical analyses reveal a non-canonical 1:2 stoichiometry between Rab14:RCP in dilute solutions, in contrast to Rab11/25 complexes. The structure of Rab14:RCP reveals that Rab14 interacts with the canonical RBD, and also provides insight into the unusual properties of the complex. Finally, we show that both the Rab Coupling Protein and Rab14 function in neuritogenesis. Structure-Function Analyses of the Interactions Between Rab11 and Rab14 Small GTPases with their Shared Effector Rab Coupling Protein (RCP).,Lall P, Lindsay A, Hanscom S, Kecman T, Taglauer ES, McVeigh UM, Franklin E, McCaffrey MW, Khan AR J Biol Chem. 2015 May 31. pii: jbc.M114.612366. PMID:26032412[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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