2dwg
RUN domain of Rap2 interacting protein x, crystallized in P2(1)2(1)2(1) space group
Structural highlights
FunctionRUFY3_MOUSE Implicated in the formation of a single axon by developing neurons. May inhibit the formation of additional axons by inhibition of PI3K in minor neuronal processes (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedRap2-interacting protein x (RPIPx) is a homolog of RPIP8, a specific effector of Rap2 GTPase. The N-terminal region of RPIP8, which contains the RUN domain, interacts with Rap2. Using cell-free synthesis and NMR, we determined that the region encompassing residues 83-255 of mouse RPIPx, which is 40-residues larger than the predicted RUN domain (residues 113-245), is the minimum fragment that forms a correctly folded protein. This fragment, the RPIPx RUN domain, interacted specifically with Rap2B in vitro in a nucleotide-dependent manner. The crystal structure of the RPIPx RUN domain was determined at 2.0 A of resolution by the multiwavelength anomalous dispersion (MAD) method. The RPIPx RUN domain comprises eight anti-parallel alpha-helices, which form an extensive hydrophobic core, followed by an extended segment. The residues in the core region are highly conserved, suggesting the conservation of the RUN domain-fold among the RUN domain-containing proteins. The residues forming a positively charged surface are conserved between RPIP8 and its homologs, suggesting that this surface is important for Rap2 binding. In the crystal the putative Rap2 binding site of the RPIPx RUN domain interacts with the extended segment in a segment-swapping manner. Crystal structure of the RUN domain of the RAP2-interacting protein x.,Kukimoto-Niino M, Takagi T, Akasaka R, Murayama K, Uchikubo-Kamo T, Terada T, Inoue M, Watanabe S, Tanaka A, Hayashizaki Y, Kigawa T, Shirouzu M, Yokoyama S J Biol Chem. 2006 Oct 20;281(42):31843-53. Epub 2006 Aug 23. PMID:16928684[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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