6k4l
Crystal structure of Se-labelled SidJ complex with CaM at 2.95 ACrystal structure of Se-labelled SidJ complex with CaM at 2.95 A
Structural highlights
Disease[CALM1_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14. Function[CALM1_HUMAN] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).[1] [2] [3] [4] Publication Abstract from PubMedThe bacterial pathogen Legionella pneumophila creates an intracellular niche permissive for its replication by extensively modulating host cell functions using hundreds of effector proteins delivered via its Dot/Icm secretion system(1). Among these, members of the SidE family (SidEs) regulate multiple cellular processes by a unique phosphoribosyl ubiquitination mechanism that bypasses the canonical ubiquitination machinery(2-4). The activity of SidEs is regulated by SidJ, another Dot/Icm effector(5), but the mechanism of such regulation is not completely understood(6,7). Here we demonstrate that SidJ inhibits the activity of SidEs by inducing covalent attachment of glutamate moieties to E860 of SdeA, which is one of the catalytic residues for the mono-ADP-ribosyltransferase activity involved in ubiquitin activation(2). The inhibition by SidJ is spatially restricted in host cells because its activity requires the eukaryote-specific protein calmodulin (CaM). We solved a structure of SidJ-CaM in complex with adenosine monophosphate (AMP) and found that the ATP utilized is cleaved at the alpha phosphate position by SidJ which in the absence of glutamate or modifiable SdeA undergoes self-AMPylation. Our results reveal an unprecedented mechanism of regulation in bacterial pathogenicity in which a glutamylation reaction that inhibits the activity of virulence factors is activated by host factor-dependent acyl-adenylation. Regulation of phosphoribosyl ubiquitination by a calmodulin-dependent glutamylase.,Gan N, Zhen X, Liu Y, Xu X, He C, Qiu J, Liu Y, Fujimoto GM, Nakayasu ES, Zhou B, Zhao L, Puvar K, Das C, Ouyang S, Luo ZQ Nature. 2019 Jul 22. pii: 10.1038/s41586-019-1439-1. doi:, 10.1038/s41586-019-1439-1. PMID:31330531[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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