6OS4
Calmodulin in complex with farnesyl cysteine methyl ester
Summary for 6OS4
| Entry DOI | 10.2210/pdb6os4/pdb |
| Descriptor | Calmodulin-1, CALCIUM ION, s-farnesyl-l-cysteine methyl ester, ... (4 entities in total) |
| Functional Keywords | complex, lipid, translocation, metal binding protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 17221.20 |
| Authors | Grant, B.M.M.,Enomoto, M.,Lee, K.Y.,Back, S.I.,Gebregiworgis, T.,Ishiyama, N.,Ikura, M.,Marshall, C. (deposition date: 2019-05-01, release date: 2020-04-08, Last modification date: 2024-03-13) |
| Primary citation | Grant, B.M.M.,Enomoto, M.,Back, S.I.,Lee, K.Y.,Gebregiworgis, T.,Ishiyama, N.,Ikura, M.,Marshall, C.B. Calmodulin disrupts plasma membrane localization of farnesylated KRAS4b by sequestering its lipid moiety. Sci.Signal., 13:-, 2020 Cited by PubMed Abstract: KRAS4b is a small guanosine triphosphatase (GTPase) protein that regulates several signal transduction pathways that underlie cell proliferation, differentiation, and survival. KRAS4b function requires prenylation of its C terminus and recruitment to the plasma membrane, where KRAS4b activates effector proteins including the RAF family of kinases. The Ca-sensing protein calmodulin (CaM) has been suggested to regulate the localization of KRAS4b through direct, Ca-dependent interaction, but how CaM and KRAS4b functionally interact is controversial. Here, we determined a crystal structure, which was supported by solution nuclear magnetic resonance (NMR), that revealed the sequestration of the prenyl moiety of KRAS4b in the hydrophobic pocket of the C-terminal lobe of Ca-bound CaM. Our engineered fluorescence resonance energy transfer (FRET)-based biosensor probes (CaMeRAS) showed that, upon stimulation of Ca influx by extracellular ligands, KRAS4b reversibly translocated in a Ca-CaM-dependent manner from the plasma membrane to the cytoplasm in live HeLa and HEK293 cells. These results reveal a mechanism underlying the inhibition of KRAS4b activity by Ca signaling pathways. PubMed: 32234958DOI: 10.1126/scisignal.aaz0344 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.05 Å) |
Structure validation
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