4D0G

Structure of Rab14 in complex with Rab-Coupling Protein (RCP)

Summary for 4D0G

• Entry DOI: 10.2210/pdb4d0g/pdb
• Descriptor: RAS-RELATED PROTEIN RAB-14, RAB11 FAMILY-INTERACTING PROTEIN 1, GUANOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: hydrolase, rab14 gtpase, endosomal trafficking, rab- binding domain (rbd), effector recruitment
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Recycling endosome: P61106; Recycling endosome . Isoform 2: Cytoplasmic vesicle, phagosome membrane: Q6WKZ4
• Total number of polymer chains: 2
• Total formula weight: 28335.23

Authors

Lall, P.,Khan, A.R. (deposition date: 2014-04-25, release date: 2015-05-20, Last modification date: 2024-10-16)

Primary citation

Lall, P.,Lindsay, A.J.,Hanscom, S.,Kecman, T.,Taglauer, E.S.,Mcveigh, U.M.,Franklin, E.,Mccaffrey, M.W.,Khan, A.R.
Structure-Function Analyses of the Interactions between Rab11 and Rab14 Small Gtpases with Their Shared Effector Rab Coupling Protein (Rcp).
J.Biol.Chem., 290:18817-, 2015

PubMed Abstract: Rab GTPases recruit effector proteins, via their GTP-dependent switch regions, to distinct subcellular 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 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 noncanonical 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 Rab-binding domain 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.

PubMed: 26032412
DOI: 10.1074/JBC.M114.612366

Experimental method

X-RAY DIFFRACTION (2.5 Å)