4QLR

Llama nanobody n02 raised against EAEC T6SS TssM

4QLR の概要

• エントリーDOI: 10.2210/pdb4qlr/pdb
• 関連するPDBエントリー: 4QGY
• 分子名称: Llama nanobody n02 VH domain (2 entities in total)
• 機能のキーワード: nanobody, immunoglobulin domain, t6ss tssm, immune system
• 由来する生物種: Lama glama
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28579.10

構造登録者

Nguyen, V.S.,Desmyter, A.,Le, T.T.H.,Durand, E.,Kellenberger, C.,Douzi, B.,Spinelli, S.,Cascales, E.,Cambillau, C.,Roussel, A. (登録日: 2014-06-13, 公開日: 2015-04-08, 最終更新日: 2024-10-16)

主引用文献

Nguyen, V.S.,Logger, L.,Spinelli, S.,Desmyter, A.,Le, T.T.,Kellenberger, C.,Douzi, B.,Durand, E.,Roussel, A.,Cascales, E.,Cambillau, C.
Inhibition of Type VI Secretion by an Anti-TssM Llama Nanobody.
Plos One, 10:e0122187-e0122187, 2015

PubMed Abstract: The type VI secretion system (T6SS) is a secretion pathway widespread in Gram-negative bacteria that targets toxins in both prokaryotic and eukaryotic cells. Although most T6SSs identified so far are involved in inter-bacterial competition, a few are directly required for full virulence of pathogens. The T6SS comprises 13 core proteins that assemble a large complex structurally and functionally similar to a phage contractile tail structure anchored to the cell envelope by a trans-membrane spanning stator. The central part of this stator, TssM, is a 1129-amino-acid protein anchored in the inner membrane that binds to the TssJ outer membrane lipoprotein. In this study, we have raised camelid antibodies against the purified TssM periplasmic domain. We report the crystal structure of two specific nanobodies that bind to TssM in the nanomolar range. Interestingly, the most potent nanobody, nb25, competes with the TssJ lipoprotein for TssM binding in vitro suggesting that TssJ and the nb25 CDR3 loop share the same TssM binding site or causes a steric hindrance preventing TssM-TssJ complex formation. Indeed, periplasmic production of the nanobodies displacing the TssM-TssJ interaction inhibits the T6SS function in vivo. This study illustrates the power of nanobodies to specifically target and inhibit bacterial secretion systems.

PubMed: 25811612
DOI: 10.1371/journal.pone.0122187

実験手法

X-RAY DIFFRACTION (1.7 Å)