+
データを開く
-
基本情報
登録情報 | データベース: PDB / ID: 6vx4 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
タイトル | Density-fitted Model Structure of Antibody Variable Domains of TyTx11 in Complex with Typhoid Toxin | ||||||||||||
![]() |
| ||||||||||||
![]() | TOXIN / Typhoid Toxin / A2B5 / Antibody / Fab | ||||||||||||
機能・相同性 | ![]() 転移酵素; グリコシル基を移すもの; 五炭糖残基を移すもの / : / NAD+ ADP-ribosyltransferase activity / toxin activity / endonuclease activity / 加水分解酵素; エステル加水分解酵素 / hydrolase activity / extracellular region 類似検索 - 分子機能 | ||||||||||||
生物種 | ![]() ![]() ![]() | ||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.12 Å | ||||||||||||
![]() | Nguyen, T. / Song, J. | ||||||||||||
資金援助 | ![]()
| ||||||||||||
![]() | ![]() タイトル: Mechanisms of typhoid toxin neutralization by antibodies targeting glycan receptor binding and nuclease subunits. 著者: Changhwan Ahn / Yi-An Yang / Durga P Neupane / Tri Nguyen / Angelene F Richards / Ji Hyun Sim / Nicholas J Mantis / Jeongmin Song / ![]() 要旨: Nearly all clinical isolates of Typhi, the cause of typhoid fever, are antibiotic resistant. All Typhi isolates secrete an AB exotoxin called typhoid toxin to benefit the pathogen during infection. ...Nearly all clinical isolates of Typhi, the cause of typhoid fever, are antibiotic resistant. All Typhi isolates secrete an AB exotoxin called typhoid toxin to benefit the pathogen during infection. Here, we demonstrate that antibiotic-resistant Typhi secretes typhoid toxin continuously during infection regardless of antibiotic treatment. We characterize typhoid toxin antibodies targeting glycan-receptor-binding PltB or nuclease CdtB, which neutralize typhoid toxin and , as demonstrated by using typhoid toxin secreted by antibiotic-resistant Typhi during human cell infection and lethal dose typhoid toxin challenge to mice. TyTx11 generated in this study neutralizes typhoid toxin effectively, comparable to TyTx4 that binds to all PltB subunits available per holotoxin. Cryoelectron microscopy explains that the binding of TyTx11 to CdtB makes this subunit inactive through CdtB catalytic-site conformational change. The identified toxin-neutralizing epitopes are conserved across all Typhi clinical isolates, offering critical insights into typhoid toxin-neutralizing strategies. | ||||||||||||
履歴 |
|
-
構造の表示
ムービー |
![]() |
---|---|
構造ビューア | 分子: ![]() ![]() |
-
ダウンロードとリンク
-
ダウンロード
PDBx/mmCIF形式 | ![]() | 223.7 KB | 表示 | ![]() |
---|---|---|---|---|
PDB形式 | ![]() | 184.4 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.1 MB | 表示 | ![]() |
---|---|---|---|---|
文書・詳細版 | ![]() | 1.1 MB | 表示 | |
XML形式データ | ![]() | 46.1 KB | 表示 | |
CIF形式データ | ![]() | 70.1 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
-
リンク
-
集合体
登録構造単位 | ![]()
|
---|---|
1 |
|
-
要素
#1: 抗体 | 分子量: 11689.935 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() | ||||||
---|---|---|---|---|---|---|---|
#2: タンパク質 | 分子量: 12563.042 Da / 分子数: 5 / 由来タイプ: 組換発現 由来: (組換発現) ![]() 遺伝子: pltB, D4F19_07865, D4F39_13740, D4G09_02615, D4X81_03235, D5848_06295, D5891_16360, D5B50_14740, D5C10_10475, D6331_06440, D6K86_15515, D6P24_09080, D6Q71_07195, D7N07_01470, D8R98_02600, ...遺伝子: pltB, D4F19_07865, D4F39_13740, D4G09_02615, D4X81_03235, D5848_06295, D5891_16360, D5B50_14740, D5C10_10475, D6331_06440, D6K86_15515, D6P24_09080, D6Q71_07195, D7N07_01470, D8R98_02600, D8S38_09485, DL104_04040, DLF44_02615, DM364_15630, DMA85_08120, DMV05_17400, DN022_06665, DN116_07470, DN223_02675, DNJ32_13915, DNL67_05455, DNM39_02515, DNV82_15785, DNV95_15160, DOH59_08615, DP757_14390, DPC06_03915, DPJ15_14935, DPS97_10830, DQ802_09840, DQD72_07750, DQJ57_09285, DRE79_02610, DRW87_14355, DRX58_02590, DRX79_07315, DS260_02735, DS269_05775, DS339_07525, DS529_00005, DSM93_00460, DST18_05335, DTV88_06700, DU090_09370, DUQ83_10880, DUW14_00135, DVF55_05015, EDK96_01785, EIT32_03595, EIT43_00570, YL55_10165 発現宿主: ![]() ![]() #3: 抗体 | | 分子量: 20049.723 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() #4: タンパク質 | | 分子量: 25117.145 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) ![]() 遺伝子: artA, CIJ14_23170, D4382_23660, D4E24_23260, D4Y21_22940, D5806_21720, D6Q50_22735, D9Q66_22850, DJ817_22925, DJ902_22835, DKA33_22665, DOG98_22205, DP807_22355, DPD01_22815, DPO73_22750, ...遺伝子: artA, CIJ14_23170, D4382_23660, D4E24_23260, D4Y21_22940, D5806_21720, D6Q50_22735, D9Q66_22850, DJ817_22925, DJ902_22835, DKA33_22665, DOG98_22205, DP807_22355, DPD01_22815, DPO73_22750, DQ973_22620, DQC14_23005, DQC85_22640, DQS90_22840, EDL32_22840, EGM32_22620, EIW71_22495, PltA 発現宿主: ![]() ![]() #5: タンパク質 | | 分子量: 28149.777 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) ![]() 遺伝子: cdtB, ABO08_07050, ACK79_04015, ACS18_04320, ADQ64_04510, AF726_04075, AG53_02460, AH360_09375, AH874_08650, AHN91_05150, AHS86_01310, AHX56_04670, AHY46_21185, AIA22_01750, AID13_25040, ...遺伝子: cdtB, ABO08_07050, ACK79_04015, ACS18_04320, ADQ64_04510, AF726_04075, AG53_02460, AH360_09375, AH874_08650, AHN91_05150, AHS86_01310, AHX56_04670, AHY46_21185, AIA22_01750, AID13_25040, ALX58_21685, AU833_04405, AU920_00110, AXO05_06525, BXD49_09845, BXO48_02100, C3O10_15300, CIJ14_23185, D4382_23675, D4E01_03970, D4E24_23275, D4E82_03815, D4X65_01210, D4Y21_22955, D4Y61_01580, D5769_01120, D5773_04415, D5806_21735, D5905_00655, D5938_05180, D5A94_07255, D5B66_02920, D5P52_03820, D5W53_03345, D5X56_14350, D6J84_12220, D6Q32_04050, D6Q48_23450, D6Q50_22750, D6R14_01875, D6S47_01810, D6S52_04640, D7M89_03925, D7O59_01230, D8Q95_07260, D8R18_22625, D8R28_03780, D8R78_05465, D8S31_11805, D9P30_01530, D9P43_07260, D9Q66_22865, DAX91_01380, DJ817_22940, DJ902_22850, DK094_15420, DK681_22625, DK719_00065, DKA33_22680, DKS84_01205, DKT00_12650, DL111_03690, DLB36_01945, DLC21_01190, DM347_00605, DM358_02585, DMA89_03440, DML97_01185, DMM24_06680, DMU80_01195, DMU94_00450, DMV34_24005, DN115_03160, DN181_02750, DN218_09840, DN257_00960, DNM18_03225, DNP18_20975, DNU33_00605, DNU46_06990, DNV11_08545, DNV24_09060, DNV84_01240, DNZ24_19360, DNZ91_01190, DO736_07435, DO994_18310, DOA32_23160, DOC12_13865, DOC15_02915, DOC34_02235, DOG98_22220, DOH12_03665, DOQ73_02885, DOR42_02915, DOR52_05945, DOW79_02275, DOX21_23175, DP728_08755, DP748_00630, DP792_04070, DP807_22370, DP838_14200, DPC30_05570, DPD01_22830, DPD54_23140, DPE66_01635, DPE90_12380, DPJ07_11775, DPK35_02680, DPO73_22765, DPR96_19355, DPS68_01210, DPT88_22945, DPZ91_06800, DQ837_03030, DQ973_22635, DQ986_03355, DQC14_23020, DQC85_22655, DQJ66_20360, DQJ71_17745, DQK72_01185, DQR07_01185, DQS17_02890, DQS90_22855, DQY62_02055, DQZ13_01205, DRA30_01205, DRF26_01185, DRK15_02285, DRK71_19590, DRK91_13535, DRL63_05765, DRM75_04210, DRT15_23155, DRU74_02985, DRV60_04480, DRX43_08215, DRY73_10160, DRZ18_10315, DS251_02230, DS368_09485, DS470_09640, DS570_05080, DS689_07420, DSA82_02305, DSA99_17640, DSF62_00555, DSQ94_23515, DTE82_23795, DTF17_02235, DTF39_05055, DTG02_04520, DTG24_03875, DTG49_09625, DTG90_25155, DTH05_08145, DTT89_00540, DTU25_03425, DTW06_03295, DU078_23475, DU168_00610, DU852_01200, DU949_19355, DUA52_03235, DUC30_24990, DUE02_01595, DUP59_10365, DUQ37_03210, DUQ73_01530, DUR82_01195, DUR89_07585, DUU35_01075, DUU43_23100, DUU47_01595, DUV63_05900, DVF01_11150, EBC34_19090, EBC39_01055, ECA57_07075, ED432_03555, EDL32_22855, EGM22_03890, EGM32_22635, EHB26_00195, EHD17_22415, EHF16_02745, EIW64_10595, EIW71_22510, EIW76_01180, GX90_01205, JF03_03615, KO25_07020, LB54_02820, NCTC8272_01874, QC88_03775, R126_05570, R133_02035, RY52_03905, YR14_00925, ZG82_07355 発現宿主: ![]() ![]() 参照: UniProt: A0A447PE99, UniProt: Q8Z6A7*PLUS, 加水分解酵素; エステル加水分解酵素 |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-
試料調製
構成要素 |
| ||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
分子量 |
| ||||||||||||||||||||||||||||
由来(天然) |
| ||||||||||||||||||||||||||||
由来(組換発現) |
| ||||||||||||||||||||||||||||
緩衝液 | pH: 7.5 | ||||||||||||||||||||||||||||
緩衝液成分 |
| ||||||||||||||||||||||||||||
試料 | 濃度: 0.2 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: Freshly prepared size-exclusion-chromatography purified complex of TyTx11 IgG and Typhoid toxin wild-type | ||||||||||||||||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277.15 K / 詳細: blot for 2.0 second before plunging |
-
電子顕微鏡撮影
実験機器 | ![]() モデル: Talos Arctica / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TALOS ARCTICA |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 63000 X / 最大 デフォーカス(公称値): 1500 nm / 最小 デフォーカス(公称値): 800 nm / Cs: 2.7 mm / C2レンズ絞り径: 50 µm |
試料ホルダ | 凍結剤: NITROGEN |
撮影 | 電子線照射量: 54.7 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
電子光学装置 | エネルギーフィルター名称: GIF Bioquantum / エネルギーフィルタースリット幅: 20 eV |
-
解析
ソフトウェア | 名称: PHENIX / バージョン: dev_3765: / 分類: 精密化 | ||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EMソフトウェア |
| ||||||||||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.12 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 61478 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||
原子モデル構築 | 詳細: Initial local fitting was done using Chimera and then Coot was used for rebuilding Fab variable domains into correct sequences. Refinement was performed using Real Space Refine in PHENIX and ...詳細: Initial local fitting was done using Chimera and then Coot was used for rebuilding Fab variable domains into correct sequences. Refinement was performed using Real Space Refine in PHENIX and was iterated with manual building in Coot. | ||||||||||||||||||||||||||||||||
原子モデル構築 |
| ||||||||||||||||||||||||||||||||
拘束条件 |
|