2c7m
From Proteopedia
Human Rabex-5 residues 1-74 in complex with Ubiquitin
Structural highlights
FunctionRABX5_HUMAN Rab effector protein acting as linker between gamma-adaptin, RAB4A or RAB5A. Involved in endocytic membrane fusion and membrane trafficking of recycling endosomes. Stimulates nucleotide exchange on RAB5A. Can act as a ubiquitin ligase (By similarity).[1] [2] [3] Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe interaction between ubiquitinated proteins and intracellular proteins harboring ubiquitin binding domains (UBDs) is critical to a multitude of cellular processes. Here, we report that Rabex-5, a guanine nucleotide exchange factor for Rab5, binds to Ub through two independent UBDs. These UBDs determine a number of properties of Rabex-5, including its coupled monoubiquitination and interaction in vivo with ubiquitinated EGFRs. Structural and biochemical characterization of the UBDs of Rabex-5 revealed that one of them (MIU, motif interacting with ubiquitin) binds to Ub with modes superimposable to those of the UIM (ubiquitin-interacting motif):Ub interaction, although in the opposite orientation. The other UBD, RUZ (Rabex-5 ubiquitin binding zinc finger) binds to a surface of Ub centered on Asp58(Ub) and distinct from the "canonical" Ile44(Ub)-based surface. The two binding surfaces allow Ub to interact simultaneously with different UBDs, thus opening new perspectives in Ub-mediated signaling. Crystal structure of the ubiquitin binding domains of rabex-5 reveals two modes of interaction with ubiquitin.,Penengo L, Mapelli M, Murachelli AG, Confalonieri S, Magri L, Musacchio A, Di Fiore PP, Polo S, Schneider TR Cell. 2006 Mar 24;124(6):1183-95. Epub 2006 Feb 23. PMID:16499958[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Bos taurus | Homo sapiens | Large Structures | Confalioneri S | Di Fiore PP | Magri L | Mapelli M | Murachelli AG | Musacchio A | Penengo L | Polo S | Schneider TR