National Institutes of Health/Office of the Director
1S10OD018111
米国
National Institutes of Health/National Center for Research Resources (NIH/NCRR)
1S10RR23057
米国
National Science Foundation (NSF, United States)
DMR-1548924
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI103182
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R33AI119721
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI007323
米国
引用
ジャーナル: Nat Commun / 年: 2025 タイトル: Structures of Native Doublet Microtubules from Trichomonas vaginalis Reveal Parasite-Specific Proteins. 著者: Alexander Stevens / Saarang Kashyap / Ethan H Crofut / Shuqi E Wang / Katherine A Muratore / Patricia J Johnson / Z Hong Zhou / 要旨: Doublet microtubules (DMTs) are flagellar components required for the protist Trichomonas vaginalis (Tv) to swim through the human genitourinary tract to cause trichomoniasis, the most common non- ...Doublet microtubules (DMTs) are flagellar components required for the protist Trichomonas vaginalis (Tv) to swim through the human genitourinary tract to cause trichomoniasis, the most common non-viral sexually transmitted disease. Lack of structures of Tv's DMT (Tv-DMT) has prevented structure-guided drug design to manage Tv infection. Here, we determine the 16 nm, 32 nm, 48 nm and 96 nm-repeat structures of native Tv-DMT at resolution ranging from 3.4 to 4.4 Å by cryogenic electron microscopy (cryoEM) and built an atomic model for the entire Tv-DMT. These structures show that Tv-DMT is composed of 30 different proteins, including the α- and β-tubulin, 19 microtubule inner proteins (MIPs) and 9 microtubule outer proteins. While the A-tubule of Tv-DMT is simplistic compared to DMTs of other organisms, the B-tubule of Tv-DMT features parasite-specific proteins, such as TvFAP40 and TvFAP35. Notably, TvFAP40 and TvFAP35 form filaments near the inner and outer junctions, respectively, and interface with stabilizing MIPs. This atomic model of the Tv-DMT highlights diversity of eukaryotic motility machineries and provides a structural framework to inform rational design of therapeutics against trichomoniasis.
全体 : Radial spoke head from Flagella of T. vaginalis
全体
名称: Radial spoke head from Flagella of T. vaginalis
要素
複合体: Radial spoke head from Flagella of T. vaginalis
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超分子 #1: Radial spoke head from Flagella of T. vaginalis
超分子
名称: Radial spoke head from Flagella of T. vaginalis / タイプ: complex / ID: 1 / 親要素: 0 詳細: generated from isolation of doublet microtubules of T. vaginalis
由来(天然)
生物種: Trichomonas vaginalis G3 (ちつほねまくむし)
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実験情報
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構造解析
手法
クライオ電子顕微鏡法
解析
単粒子再構成法
試料の集合状態
particle
-
試料調製
緩衝液
pH: 7.4 構成要素:
濃度
式
名称
150.0 mM
NaCl
sodium chloride
50.0 mM
C4H11NO3
Tris
2.0 mM
MgCl2
magnesium chloride
1.0 mM
C4H10O2S2
dithiothreitol
5.0 mM
C10H16N5O13P3
adenosine triphosphate
詳細: 150 mM NaCl, 50 mM Tris, 2 mM MgCl2, 1 mM DTT, 5 mM ATP 1 x complete protease inhibitor, pH 7.4