![]() Thus, the scaffold proteins play a crucial role in the signal transduction.Īlthough various signaling pathways are the central topics in many biological fields, researchers pay much less attention on the scaffold proteins. They enhance signaling specificity or increase the signaling efficiency by increasing the local concentration of signaling components. One central role of scaffold proteins is to coordinate feedback loops in signaling pathways, and thus to regulate the signaling response. These proteins mediate a linear pathway among many partner proteins, and mediate pathway branching to multiple outputs as well. The scaffold proteins link multiple signaling proteins together to facilitate signal transduction. The spatial organization achieves high efficacy information transfer on cellular information flow. For example, scaffold protein Ste5 tethers multiple protein kinases in the MAP kinase cascade, such as Ste11, Ste7 and Fus3. More than 20 years ago, the first set of scaffold proteins were discovered, which assemble components of diverse pathways at the plasma membrane or subcellular compartments. How can signaling proteins interact with the correct partners and avoid wrong proteins? One principle is that cells achieve well in the signal transduction networks by tethering subset proteins in space and time. With maintained up-to-date data, ScaPD ( ) will be a valuable resource for understanding how individual signaling pathways are regulated.Ībout 10% of proteins expressed in human cells are involved in the signal transduction. Manually curated and predicted scaffold protein data will be a foundation for further investigation of the scaffold protein in the signal transduction. The database allows users to search, navigate and download the scaffold protein-mediated signaling networks. It currently contains 273 scaffold proteins and 1118 associated signaling pathways. Here, we have developed a user-friendly database, ScaPD, to describe computationally predicted, experimentally validated scaffold proteins and associated signaling pathways. While many databases document the signaling pathways, few databases are devoted to the scaffold proteins that medicate signal transduction. and B.C.).Scaffold proteins play a critical role in an increasing number of biological signaling processes, including simple tethering mechanism, regulating selectivity in pathways, shaping cellular behaviors. and B.C.) and European Research Council grant 716058 (K.M.C. and B.C.) Swiss National Center of Competence in Chemical Biology (K.M.C. and B.C.) Swiss National Center of Competence for Molecular Systems Engineering (K.M.C. and J.-H.C.) Swiss National Science Foundation (K.M.C. and D.T.) Amgen (S.L.) the Human Frontier Science Program Cross Disciplinary Fellowship (LT000395/2020-C) and EMBO Non-Stipendiary Fellowship (ALTF 1047-2019) (L.F.M.) the EMBO Fellowship (ALTF 191-2021) (T.S.) European Molecular Biology Organization Grant (ALTF 139-2018) (B.I.M.W.) the “la Caixa” Foundation (M.E.) the National Institute of Allergy and Infectious Diseases (NIAID) Federal Contract HHSN272201700059C (I.A.), NIH grant DP5OD026389 (S.O.) the National Science Foundation MCB 2032259 (S.O.) the Howard Hughes Medical Institute (D.B., R.R., and K.M.C.), the National Institute on Aging grant 5U19AG065156 (D.B., J.L.W., D.R.H., and M.E.) the National Cancer Institute grant R01CA240339 (D.B. and W.Y.) the DARPA Harnessing Enzymatic Activity for Lifesaving Remedies project HR001120S0052 contract HR-0012 (N.B.) the Washington Research Foundation (J.W.) the Open Philanthropy Project Improving Protein Design Fund (D.B. and J.D.) Eric and Wendy Schmidt by recommendation of the Schmidt Futures (D.J.) the DARPA Synergistic Discovery and Design project HR001117S0003 contract FA8750-17-C-0219 (D.B. This work was supported with funds provided by the Audacious Project at the Institute for Protein Design (D.B. Wicky, Andrew Muenks, Frank DiMaio, Bruno Correia, Sergey Ovchinnikov, and David Baker +21 authors +19 authors +14 authors fewer Authors Info & Affiliationsįunding: We thank Microsoft for support and for providing Azure computing resources. Hicks, Marc Expòsit, Thomas Schlichthaerle, Jung-Ho Chun, Justas Dauparas, Nathaniel Bennett, Basile I. Milles, , Minkyung Baek, Ivan Anishchenko, Wei Yang, Derrick R. Castro, Robert Ragotte, Amijai Saragovi, Lukas F. Jue Wang, Sidney Lisanza, , David Juergens, Doug Tischer, , Joseph L.
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