6ENT

Structure of the rat RKIP variant delta143-146

Summary for 6ENT

• Entry DOI: 10.2210/pdb6ent/pdb
• Related: 6ENS
• Descriptor: Phosphatidylethanolamine-binding protein 1, ZINC ION, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: rkip, pebp, pbp, signaling protein
• Biological source: Rattus norvegicus (Rat)
• Cellular location: Cytoplasm: P31044
• Total number of polymer chains: 1
• Total formula weight: 21313.68

Authors

Koelmel, W.,Hirschbeck, M.,Schindelin, H.,Lorenz, K.,Kisker, C. (deposition date: 2017-10-06, release date: 2017-12-13, Last modification date: 2024-01-17)

Primary citation

Skinner, J.J.,Wang, S.,Lee, J.,Ong, C.,Sommese, R.,Sivaramakrishnan, S.,Koelmel, W.,Hirschbeck, M.,Schindelin, H.,Kisker, C.,Lorenz, K.,Sosnick, T.R.,Rosner, M.R.
Conserved salt-bridge competition triggered by phosphorylation regulates the protein interactome.
Proc. Natl. Acad. Sci. U.S.A., 114:13453-13458, 2017

PubMed Abstract: Phosphorylation is a major regulator of protein interactions; however, the mechanisms by which regulation occurs are not well understood. Here we identify a salt-bridge competition or "theft" mechanism that enables a phospho-triggered swap of protein partners by Raf Kinase Inhibitory Protein (RKIP). RKIP transitions from inhibiting Raf-1 to inhibiting G-protein-coupled receptor kinase 2 upon phosphorylation, thereby bridging MAP kinase and G-Protein-Coupled Receptor signaling. NMR and crystallography indicate that a phosphoserine, but not a phosphomimetic, competes for a lysine from a preexisting salt bridge, initiating a partial unfolding event and promoting new protein interactions. Structural elements underlying the theft occurred early in evolution and are found in 10% of homo-oligomers and 30% of hetero-oligomers including Bax, Troponin C, and Early Endosome Antigen 1. In contrast to a direct recognition of phosphorylated residues by binding partners, the salt-bridge theft mechanism represents a facile strategy for promoting or disrupting protein interactions using solvent-accessible residues, and it can provide additional specificity at protein interfaces through local unfolding or conformational change.

PubMed: 29208709
DOI: 10.1073/pnas.1711543114

Experimental method

X-RAY DIFFRACTION (2.66 Å)