4BG6
14-3-3 interaction with Rnd3 prenyl-phosphorylation motif
Summary for 4BG6
Entry DOI | 10.2210/pdb4bg6/pdb |
Descriptor | 14-3-3 PROTEIN ZETA/DELTA, RHO-RELATED GTP-BINDING PROTEIN RHOE, 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL, ... (5 entities in total) |
Functional Keywords | signaling protein, prenylation, actin cytoskeleton |
Biological source | HOMO SAPIENS (HUMAN) More |
Total number of polymer chains | 4 |
Total formula weight | 59524.94 |
Authors | Riou, P.,Kjaer, S.,Purkiss, A.,O'Reilly, N.,McDonald, N.Q. (deposition date: 2013-03-23, release date: 2013-05-29, Last modification date: 2024-11-20) |
Primary citation | Riou, P.,Kjaer, S.,Garg, R.,Purkiss, A.,George, R.,Cain, R.J.,Bineva, G.,Reymond, N.,Mccoll, B.,Thompson, A.J.,O'Reilly, N.,Mcdonald, N.Q.,Parker, P.J.,Ridley, A.J. 14-3-3 Proteins Interact with a Hybrid Prenyl-Phosphorylation Motif to Inhibit G Proteins. Cell(Cambridge,Mass.), 153:640-, 2013 Cited by PubMed Abstract: Signaling through G proteins normally involves conformational switching between GTP- and GDP-bound states. Several Rho GTPases are also regulated by RhoGDI binding and sequestering in the cytosol. Rnd proteins are atypical constitutively GTP-bound Rho proteins, whose regulation remains elusive. Here, we report a high-affinity 14-3-3-binding site at the C terminus of Rnd3 consisting of both the Cys241-farnesyl moiety and a Rho-associated coiled coil containing protein kinase (ROCK)-dependent Ser240 phosphorylation site. 14-3-3 binding to Rnd3 also involves phosphorylation of Ser218 by ROCK and/or Ser210 by protein kinase C (PKC). The crystal structure of a phosphorylated, farnesylated Rnd3 peptide with 14-3-3 reveals a hydrophobic groove in 14-3-3 proteins accommodating the farnesyl moiety. Functionally, 14-3-3 inhibits Rnd3-induced cell rounding by translocating it from the plasma membrane to the cytosol. Rnd1, Rnd2, and geranylgeranylated Rap1A interact similarly with 14-3-3. In contrast to the canonical GTP/GDP switch that regulates most Ras superfamily members, our results reveal an unprecedented mechanism for G protein inhibition by 14-3-3 proteins. PubMed: 23622247DOI: 10.1016/J.CELL.2013.03.044 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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