Genetic determination of essential residues of the Vibrio cholerae actin cross-linking domain reveals functional similarity with glutamine synthetases.
Genetic determination of essential residues of the Vibrio cholerae actin cross-linking domain reveals functional similarity with glutamine synthetases.
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DOI：
10.1111/j.1365-2958.2009.06810.x
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发表时间：
2009-09
影响因子：
3.6
通讯作者：
Satchell KJ
中科院分区：
文献类型：
--
作者：
Geissler B;Bonebrake A;Sheahan KL;Walker ME;Satchell KJ
肌动蛋白交联结构域（ACD）是在几种细菌毒素中发现的不同结构域，包括霍乱弧菌MARTX毒素。霍乱弧菌的ACD（ACDVc）以ATP和Mg/Mn 2+依赖的方式催化两个肌动蛋白分子上的赖氨酸50和谷氨酸270之间形成不可逆的异肽键。在体内，交联耗尽G-肌动蛋白的细胞池，导致肌动蛋白细胞骨架解聚。虽然由这些效应结构域进行的肌动蛋白交联反应已被显著表征，但由于缺乏与已知蛋白质的显著同源性，ACDVc催化位点仍然难以捉摸。使用多种遗传学方法，我们已经确定了ACDVc的区域和氨基酸所需的完整的肌动蛋白交联活性。然后，使用这些功能数据和结构同源性预测，确定了被证明对ACDVc活性重要的几个残基与谷氨酰胺合成酶家族的酶的活性位点残基保守。因此，ACD是细菌毒素效应子的家族，其可能在进化上与参与氨基酸生物合成的连接酶相关。
Actin cross-linking domains (ACD) are distinct domains found in several bacterial toxins, including the Vibrio cholerae MARTX toxin. The ACD of V. cholerae (ACDVc) catalyzes the formation of an irreversible iso-peptide bond between lysine 50 and glutatmic acid 270 on two actin molecules in an ATP and Mg/Mn2+-dependent manner. In vivo, cross-linking depletes the cellular pool of G-actin leading to actin cytoskeleton depolymerization. While the actin cross-linking reaction performed by these effector domains has been significantly characterized, the ACDVc catalytic site has remained elusive due to lack of significant homology to known proteins. Using multiple genetic approaches, we have identified regions and amino acids of ACDVc required for full actin cross-linking activity. Then, using these functional data and structural homology predictions, it was determined that several residues demonstrated to be important for ACDVc activity are conserved with active site residues of the glutamine synthetase family of enzymes. Thus, the ACDs are a family of bacterial toxin effectors that may be evolutionarily related to ligases involved in amino acid biosynthesis.
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影响因子：
11.4
作者：
Fullner, KJ;Mekalanos, JJ
通讯作者：
Mekalanos, JJ
影响因子：
3
作者：
Lassmann T;Sonnhammer EL
通讯作者：
Sonnhammer EL
DOI：
10.1073/pnas.0401104101
发表时间：
2004-06-29
影响因子：
11.1
作者：
Sheahan, KL;Cordero, CL;Satchell, KJF
通讯作者：
Satchell, KJF
影响因子：
2.6
作者：
Hua, SB;Qiu, MS;Luo, Y
通讯作者：
Luo, Y
影响因子：
3.1
作者：
Rahman, M. Hasibur;Biswas, Kuntal;Faruque, Shah M.
通讯作者：
Faruque, Shah M.