5AAZ

TBK1 recruitment to cytosol-invading Salmonella induces anti- bacterial autophagy

Summary for 5AAZ

• Entry DOI: 10.2210/pdb5aaz/pdb
• Related: 5AAQ 5AAS 5AAY
• NMR Information: BMRB: 25742
• Descriptor: OPTINEURIN, ZINC ION (2 entities in total)
• Functional Keywords: protein binding
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm, perinuclear region: Q96CV9
• Total number of polymer chains: 1
• Total formula weight: 3587.56

Authors

Thurston, T.l.,Allen, M.D.,Ravenhill, B.,Karpiyevitch, M.,Bloor, S.,Kaul, A.,Matthews, S.,Komander, D.,Holden, D.,Bycroft, M.,Randow, F. (deposition date: 2015-07-31, release date: 2016-07-13, Last modification date: 2024-05-15)

Primary citation

Thurston, T.L.,Boyle, K.B.,Allen, M.,Ravenhill, B.J.,Karpiyevich, M.,Bloor, S.,Kaul, A.,Noad, J.,Foeglein, A.,Matthews, S.A.,Komander, D.,Bycroft, M.,Randow, F.
Recruitment of Tbk1 to Cytosol-Invading Salmonella Induces Wipi2-Dependent Antibacterial Autophagy.
Embo J., 35:1779-, 2016

PubMed Abstract: Mammalian cells deploy autophagy to defend their cytosol against bacterial invaders. Anti-bacterial autophagy relies on the core autophagy machinery, cargo receptors, and "eat-me" signals such as galectin-8 and ubiquitin that label bacteria as autophagy cargo. Anti-bacterial autophagy also requires the kinase TBK1, whose role in autophagy has remained enigmatic. Here we show that recruitment of WIPI2, itself essential for anti-bacterial autophagy, is dependent on the localization of catalytically active TBK1 to the vicinity of cytosolic bacteria. Experimental manipulation of TBK1 recruitment revealed that engagement of TBK1 with any of a variety of Salmonella-associated "eat-me" signals, including host-derived glycans and K48- and K63-linked ubiquitin chains, suffices to restrict bacterial proliferation. Promiscuity in recruiting TBK1 via independent signals may buffer TBK1 functionality from potential bacterial antagonism and thus be of evolutionary advantage to the host.

PubMed: 27370208
DOI: 10.15252/EMBJ.201694491

Experimental method

SOLUTION NMR