5k35
From Proteopedia
Structure of the Legionella effector, AnkB, in complex with human Skp1
Structural highlights
FunctionSKP1_HUMAN Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.[1] [2] Publication Abstract from PubMedAnkyrin B (AnkB/LegAU13) is a translocated F box effector essential for the intracellular replication of the pathogen Legionella pneumophila. AnkB co-opts a host ubiquitin ligase to decorate the pathogen-containing vacuole with K48-linked polyubiquitinated proteins and degrade host proteins as a source of energy. Here, we report that AnkB commandeers the host ubiquitin-proteasome system through mimicry of two eukaryotic protein domains. Using X-ray crystallography, we determined the 3D structure of AnkB in complex with Skp1, a component of the human SCF ubiquitination ligase. The structure confirms that AnkB contains an N-terminal F box similar to Skp2 and a C-terminal substrate-binding domain similar to eukaryotic ankyrin repeats. We identified crucial amino acids in the substrate-binding domain of AnkB and showed them to be essential for the function of AnkB in L. pneumophila intracellular proliferation. The study reveals how Legionella uses molecular mimicry to manipulate the host ubiquitination pathway and proliferate intracellularly. Structural Mimicry by a Bacterial F Box Effector Hijacks the Host Ubiquitin-Proteasome System.,Wong K, Perpich JD, Kozlov G, Cygler M, Abu Kwaik Y, Gehring K Structure. 2017 Feb 7;25(2):376-383. doi: 10.1016/j.str.2016.12.015. Epub 2017, Jan 19. PMID:28111017[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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