LegC3, an effector protein from Legionella pneumophila, inhibits homotypic yeast vacuole fusion in vivo and in vitro.
LegC3, an effector protein from Legionella pneumophila, inhibits homotypic yeast vacuole fusion in vivo and in vitro.
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DOI：
10.1371/journal.pone.0056798
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Starai VJ
中科院分区：
文献类型：
--
作者：
Bennett TL;Kraft SM;Reaves BJ;Mima J;O'Brien KM;Starai VJ
在感染过程中，细胞内致病性细菌嗜肺军团菌引起宿主膜运输途径的广泛重塑，无论是在由ER衍生的囊泡和质膜成分组成的可复制空泡的构建中，还是在正常吞噬体：内体/溶酶体融合途径的抑制中。在此，我们鉴定了来自L.在体外，嗜肺菌能够抑制SNARE和Rab GTP酶依赖性膜融合途径，即酵母液泡（溶酶体）的同型融合。这种液泡融合抑制似乎是特异性的，因为类似的分泌卷曲螺旋结构域含有蛋白质从L。pneumophila，LegC 7/YlfA和LegC 2/YlfB不抑制空泡融合。LegC 3介导的融合抑制是可逆的酵母胞质提取物，以及通过纯化的可溶性SNARE，Vam 7 p。LegC 3阻断了液泡融合过程中反式SNARE复合物的形成，尽管我们没有检测到LegC 3与融合所需的液泡SNARE蛋白复合物的直接相互作用。此外，LegC 3不能抑制空泡SNARE驱动的膜融合的定义的合成模型，进一步表明LegC 3在膜融合期间不直接抑制空泡SNARE、HOPS复合物或Sec 17 p/18 p的活性。LegC 3可能被军团菌利用来调节致病过程中的真核细胞膜融合事件。
During infection, the intracellular pathogenic bacterium Legionella pneumophila causes an extensive remodeling of host membrane trafficking pathways, both in the construction of a replication-competent vacuole comprised of ER-derived vesicles and plasma membrane components, and in the inhibition of normal phagosome:endosome/lysosome fusion pathways. Here, we identify the LegC3 secreted effector protein from L. pneumophila as able to inhibit a SNARE- and Rab GTPase-dependent membrane fusion pathway in vitro, the homotypic fusion of yeast vacuoles (lysosomes). This vacuole fusion inhibition appeared to be specific, as similar secreted coiled-coiled domain containing proteins from L. pneumophila, LegC7/YlfA and LegC2/YlfB, did not inhibit vacuole fusion. The LegC3-mediated fusion inhibition was reversible by a yeast cytosolic extract, as well as by a purified soluble SNARE, Vam7p. LegC3 blocked the formation of trans-SNARE complexes during vacuole fusion, although we did not detect a direct interaction of LegC3 with the vacuolar SNARE protein complexes required for fusion. Additionally, LegC3 was incapable of inhibiting a defined synthetic model of vacuolar SNARE-driven membrane fusion, further suggesting that LegC3 does not directly inhibit the activity of vacuolar SNAREs, HOPS complex, or Sec17p/18p during membrane fusion. LegC3 is likely utilized by Legionella to modulate eukaryotic membrane fusion events during pathogenesis.
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影响因子：
4.8
作者：
Fratti, Rutilio A.;Collins, Kevin M.;Wickner, William
通讯作者：
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影响因子：
11.4
作者：
Haas, A;Wickner, W
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影响因子：
2.5
作者：
Banuelos, M. G.;Moreno, D. E.;Gharakhanian, Editte
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DOI：
10.1073/pnas.0702290104
发表时间：
2007-05-22
影响因子：
11.1
作者：
Collins, Kevin M.;Wickner, William T.
通讯作者：
Wickner, William T.
影响因子：
4.5
作者：
Gerrard, SR;Mecklem, AB;Stevens, TH
通讯作者：
Stevens, TH