A Single Legionella Effector Catalyzes a Multistep Ubiquitination Pathway to Rearrange Tubular Endoplasmic Reticulum for Replication

被引:153
作者
Kotewicz, Kristin M. [1 ]
Ramabhadran, Vinay [1 ,3 ]
Sjoblom, Nicole [2 ]
Vogel, Joseph P. [4 ]
Haenssler, Eva [1 ,6 ]
Zhang, Mengyun [1 ]
Behringer, Jessica [5 ]
Scheck, Rebecca A. [2 ]
Isberg, Ralph R. [1 ,3 ]
机构
[1] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, 150 Harrison Ave, Boston, MA 02111 USA
[2] Tufts Univ, Dept Chem, 62 Talbot Ave, Medford, MA 02155 USA
[3] Tufts Univ, Sch Med, Howard Hughes Med Inst, 150 Harrison Ave, Boston, MA 02111 USA
[4] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA
[5] Tufts Univ, Sch Med, Genet Program, 150 Harrison Ave, Boston, MA 02111 USA
[6] Qiagen GmbH, D-40724 Hilden, Germany
关键词
ADP-RIBOSYLATION; POSTTRANSLATIONAL MODIFICATIONS; NUDIX HYDROLASES; IV SECRETION; PNEUMOPHILA; PROTEINS; PHAGOSOME; MACROPHAGES; INFECTION; MEMBRANE;
D O I
10.1016/j.chom.2016.12.007
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Intracellular pathogens manipulate host organelles to support replication within cells. For Legionella pneumophila, the bacterium translocates proteins that establish an endoplasmic reticulum (ER)-associated replication compartment. We show here that the bacterial Sde proteins target host reticulon 4 (Rtn4) to control tubular ER dynamics, resulting in tubule rearrangements as well as alterations in Rtn4 associated with the replication compartment. These rearrangements are triggered via Sde-promoted ubiquitin transfer to Rtn4, occurring almost immediately after bacterial uptake. Ubiquitin transfer requires two sequential enzymatic activities from a single Sde polypeptide: an ADP-ribosyltransferase and a nucleotidase/phosphohydrolase. The ADP-ribosylated moiety of ubiquitin is a substrate for the nucleotidase/phosphohydrolase, resulting in either transfer of ubiquitin to Rtn4 or phosphoribosylation of ubiquitin in the absence of a ubiquitination target. Therefore, a single bacterial protein drives a multi-step biochemical pathway to control ubiquitination and tubular ER function independently of the host ubiquitin machinery.
引用
收藏
页码:169 / 181
页数:13
相关论文
共 44 条
  • [2] IcmS-dependent translocation of SdeA into macrophages by the Legionella pneumophila type IV secretion system
    Bardill, JP
    Miller, JL
    Vogel, JP
    [J]. MOLECULAR MICROBIOLOGY, 2005, 56 (01) : 90 - 103
  • [3] Characterization of the catalytic site of the ADP-ribosyltransferase Clostridium botulinum C2 toxin by site-directed mutagenesis
    Barth, H
    Preiss, JC
    Hofmann, F
    Aktories, K
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (45) : 29506 - 29511
  • [4] 2 DISTINCT DEFECTS IN INTRACELLULAR GROWTH COMPLEMENTED BY A SINGLE GENETIC-LOCUS IN LEGIONELLA-PNEUMOPHILA
    BERGER, KH
    ISBERG, RR
    [J]. MOLECULAR MICROBIOLOGY, 1993, 7 (01) : 7 - 19
  • [5] Phosphoribosylation of Ubiquitin Promotes Serine Ubiquitination and Impairs Conventional Ubiquitination
    Bhogaraju, Sagar
    Kalayil, Sissy
    Liu, Yaobin
    Bonn, Florian
    Colby, Thomas
    Matic, Ivan
    Dikic, Ivan
    [J]. CELL, 2016, 167 (06) : 1636 - +
  • [6] Alveolar Macrophages and Neutrophils Are the Primary Reservoirs for Legionella pneumophila and Mediate Cytosolic Surveillance of Type IV Secretion
    Copenhaver, Alan M.
    Casson, Cierra N.
    Nguyen, Hieu T.
    Fung, Thomas C.
    Duda, Matthew M.
    Roy, Craig R.
    Shin, Sunny
    [J]. INFECTION AND IMMUNITY, 2014, 82 (10) : 4325 - 4336
  • [7] Nudix hydrolases degrade protein-conjugated ADP-ribose
    Daniels, Casey M.
    Thirawatananond, Puchong
    Ong, Shao-En
    Gabelli, Sandra B.
    Leung, Anthony K. L.
    [J]. SCIENTIFIC REPORTS, 2015, 5
  • [8] Peripheral ER structure and function
    English, Amber R.
    Zurek, Nesia
    Voeltz, Gia K.
    [J]. CURRENT OPINION IN CELL BIOLOGY, 2009, 21 (04) : 596 - 602
  • [9] Endoplasmic Reticulum Tubule Protein Reticulon 4 Associates with the Legionella pneumophila Vacuole and with Translocated Substrate Ceg9
    Haenssler, Eva
    Ramabhadran, Vinay
    Murphy, Connor S.
    Heidtman, Matthew I.
    Isberg, Ralph R.
    [J]. INFECTION AND IMMUNITY, 2015, 83 (09) : 3479 - 3489
  • [10] Legionella pneumophila Subversion of Host Vesicular Transport by SidC Effector Proteins
    Horenkamp, Florian A.
    Mukherjee, Shaeri
    Alix, Eric
    Schauder, Curtis M.
    Hubber, Andree M.
    Roy, Craig R.
    Reinisch, Karin M.
    [J]. TRAFFIC, 2014, 15 (05) : 488 - 499