Lysinoalanine cross-linking is a conserved post-translational modification in the spirochete flagellar hook.
Lysinoalanine cross-linking is a conserved post-translational modification in the spirochete flagellar hook.
复制标题
DOI：
10.1093/pnasnexus/pgad349
复制
发表时间：
2023-12
期刊：
影响因子：
--
通讯作者：
Crane, Brian R.
中科院分区：
文献类型：
--
作者：
Lynch, Michael J.;Deshpande, Maithili;Kurniyati, Kurni;Zhang, Kai;James, Milinda;Miller, Michael;Zhang, Sheng;Passalia, Felipe J.;Wunder Jr, Elsio A.;Charon, Nyles W.;Li, Chunhao;Crane, Brian R.
螺旋体可引起莱姆病、钩端螺旋体病、梅毒和其他几种人类疾病。与其他细菌不同，螺旋体鞭毛被包裹在周质空间内，在那里，鞭毛马达的作用使细丝扭曲并推动细胞体。我们以前证明了口腔病原体齿密螺旋体(TD)和莱姆病病原体伯氏疏螺旋体(BB)在组成鞭毛挂钩的FlgE蛋白的保守半胱氨酸和赖氨酸残基之间形成共价赖氨酸丙氨酸(LAL)交联。在TD中，LAL对于钩的组装是不必要的，但对于运动是必需的，可能是由于交联键的稳定作用。在这里，我们将这些发现扩展到整个门的其他具有代表性的螺旋体物种。我们证实在密螺旋体、疏螺旋体、短小螺旋体和钩端螺旋体的重组和体内来源的样品中存在LAL交联肽。用TD观察到，一株不能形成交联剂的BB突变株极大地削弱了运动能力。钩端螺旋体FlgE不保存形成Lal的半胱氨酸残基，该残基被丝氨酸取代。然而，问号钩端螺旋体FlgE也形成Lal，在Ser-179和Lys-145、Lys-148和Lys-166之间检测到几种不同的Lal亚型，从而突出了该门中物种或目的特异性差异。我们的数据显示，LAL交联物是一种跨越螺旋体门的保守和必要的翻译后修饰，因此可能是开发螺旋体特异性抗菌剂的有效靶点。
Spirochetes cause Lyme disease, leptospirosis, syphilis, and several other human illnesses. Unlike other bacteria, spirochete flagella are enclosed within the periplasmic space where the filaments distort and push the cell body by the action of the flagellar motors. We previously demonstrated that the oral pathogen Treponema denticola (Td) and Lyme disease pathogen Borreliella burgdorferi (Bb) form covalent lysinoalanine (Lal) cross-links between conserved cysteine and lysine residues of the FlgE protein that composes the flagellar hook. In Td, Lal is unnecessary for hook assembly but is required for motility, presumably due to the stabilizing effect of the cross-link. Herein, we extend these findings to other, representative spirochete species across the phylum. We confirm the presence of Lal cross-linked peptides in recombinant and in vivo-derived samples from Treponema spp., Borreliella spp., Brachyspira spp., and Leptospira spp. As was observed with Td, a mutant strain of Bb unable to form the cross-link has greatly impaired motility. FlgE from Leptospira spp. does not conserve the Lal-forming cysteine residue which is instead substituted by serine. Nevertheless, Leptospira interrogans FlgE also forms Lal, with several different Lal isoforms being detected between Ser-179 and Lys-145, Lys-148, and Lys-166, thereby highlighting species or order-specific differences within the phylum. Our data reveal that the Lal cross-link is a conserved and necessary posttranslational modification across the spirochete phylum and may thus represent an effective target for the development of spirochete-specific antimicrobials.
登录
查看更多内容
DOI：
10.1016/b978-0-323-35775-3.00007-2
发表时间：
2017-02-17
期刊：
Pathologic Basis of Veterinary Disease
影响因子：
--
作者：
Gelberg HB
通讯作者：
Gelberg HB
影响因子：
7.7
作者：
Gibson, Kimberley H.;Trajtenberg, Felipe;Sindelar, Charles Vaughn
通讯作者：
Sindelar, Charles Vaughn
DOI：
10.1007/s10482-014-0164-x
发表时间：
2014-06-01
影响因子：
2.6
作者：
Adeolu, Mobolaji;Gupta, Radhey S.
通讯作者：
Gupta, Radhey S.
影响因子：
6.4
作者：
Edmondson DG;Hu B;Norris SJ
通讯作者：
Norris SJ
影响因子：
14.8
作者：
An L;Cogan DP;Navo CD;Jiménez-Osés G;Nair SK;van der Donk WA
通讯作者：
van der Donk WA