+
データを開く
-
基本情報
登録情報 | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | The Cryo-EM structure of IL-12, receptor subunit beta-1 and receptor subunit beta-2 complex | |||||||||
![]() | It is a density map generated in C1 symmetry. The central region has a resolution close to 3 angstrom, while the peripheral region exhibited weaker density with low resolution. | |||||||||
![]() |
| |||||||||
![]() | IL-12 / IL-12RB1 / IL-12RB2 / receptor complex / CYTOKINE | |||||||||
機能・相同性 | ![]() interleukin-27 binding / interleukin-12 beta subunit binding / late endosome lumen / interleukin-23-mediated signaling pathway / regulation of tyrosine phosphorylation of STAT protein / interleukin-12 alpha subunit binding / interleukin-12 complex / interleukin-23 complex / natural killer cell activation involved in immune response / positive regulation of dendritic cell chemotaxis ...interleukin-27 binding / interleukin-12 beta subunit binding / late endosome lumen / interleukin-23-mediated signaling pathway / regulation of tyrosine phosphorylation of STAT protein / interleukin-12 alpha subunit binding / interleukin-12 complex / interleukin-23 complex / natural killer cell activation involved in immune response / positive regulation of dendritic cell chemotaxis / positive regulation of natural killer cell activation / positive regulation of lymphocyte proliferation / positive regulation of natural killer cell mediated cytotoxicity directed against tumor cell target / negative regulation of vascular endothelial growth factor signaling pathway / negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis / positive regulation of tissue remodeling / : / positive regulation of T-helper 1 type immune response / sexual reproduction / positive regulation of NK T cell activation / positive regulation of smooth muscle cell apoptotic process / positive regulation of natural killer cell mediated cytotoxicity / positive regulation of mononuclear cell proliferation / interleukin-12 receptor binding / positive regulation of memory T cell differentiation / interleukin-12 receptor complex / natural killer cell activation / T-helper cell differentiation / interleukin-23 receptor complex / Interleukin-23 signaling / negative regulation of interleukin-17 production / positive regulation of osteoclast differentiation / positive regulation of T-helper 17 type immune response / positive regulation of NK T cell proliferation / interleukin-12-mediated signaling pathway / Interleukin-12 signaling / Interleukin-35 Signalling / response to UV-B / cytokine receptor activity / positive regulation of natural killer cell proliferation / positive regulation of granulocyte macrophage colony-stimulating factor production / T-helper 1 type immune response / negative regulation of interleukin-10 production / positive regulation of activated T cell proliferation / defense response to protozoan / positive regulation of interleukin-17 production / Interleukin-10 signaling / cytokine binding / positive regulation of interleukin-10 production / positive regulation of cell adhesion / negative regulation of protein secretion / coreceptor activity / positive regulation of T-helper 17 cell lineage commitment / T cell proliferation / extrinsic apoptotic signaling pathway / positive regulation of T cell proliferation / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of defense response to virus by host / negative regulation of inflammatory response to antigenic stimulus / regulation of cytokine production / positive regulation of interleukin-12 production / cytokine activity / negative regulation of smooth muscle cell proliferation / growth factor activity / response to virus / cellular response to virus / cellular response to type II interferon / cytokine-mediated signaling pathway / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / positive regulation of T cell mediated cytotoxicity / positive regulation of type II interferon production / positive regulation of tumor necrosis factor production / cell migration / cellular response to lipopolysaccharide / Interleukin-4 and Interleukin-13 signaling / defense response to virus / defense response to Gram-negative bacterium / response to lipopolysaccharide / cell surface receptor signaling pathway / receptor complex / defense response to Gram-positive bacterium / immune response / protein heterodimerization activity / endoplasmic reticulum lumen / external side of plasma membrane / positive regulation of cell population proliferation / protein-containing complex binding / protein kinase binding / signal transduction / extracellular space / extracellular region / identical protein binding / plasma membrane / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.75 Å | |||||||||
![]() | Chen HQ / Wang XQ / Ge XF / Zeng JW / Wang JW | |||||||||
資金援助 | ![]()
| |||||||||
![]() | ![]() タイトル: Structure and assembly of the human IL-12 signaling complex. 著者: Huiqin Chen / Xiaofei Ge / Chun Li / Jianwei Zeng / Xinquan Wang / ![]() 要旨: Interleukin (IL)-12 is a heterodimeric pro-inflammatory cytokine. Our cryoelectron microscopy structure determination of human IL-12 in complex with IL-12Rβ1 and IL-12Rβ2 at a resolution of 3. ...Interleukin (IL)-12 is a heterodimeric pro-inflammatory cytokine. Our cryoelectron microscopy structure determination of human IL-12 in complex with IL-12Rβ1 and IL-12Rβ2 at a resolution of 3.75 Å reveals that IL-12Rβ2 primarily interacts with the IL-12p35 subunit via its N-terminal Ig-like domain, while IL-12Rβ1 binds to the p40 subunit with its N-terminal fibronectin III domain. This binding mode of IL-12 with its receptors is similar to that of IL-23 but shows notable differences with other cytokines. Through structural information and biochemical assays, we identified Y62, Y189, and K192 as key residues in IL-12p35, which bind to IL-12Rβ2 with high affinity and mediate IL-12 signal transduction. Furthermore, structural comparisons reveal two distinctive conformational states and structural plasticity of the heterodimeric interface in IL-12. As a result, our study advances our understanding of IL-12 signal initiation and opens up new opportunities for the engineering and therapeutic targeting of IL-12. | |||||||||
履歴 |
|
-
構造の表示
添付画像 |
---|
-
ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 398.6 MB | ![]() | |
---|---|---|---|---|
ヘッダ (付随情報) | ![]() ![]() | 19.5 KB 19.5 KB | 表示 表示 | ![]() |
画像 | ![]() | 110.3 KB | ||
Filedesc metadata | ![]() | 6.5 KB | ||
その他 | ![]() ![]() | 391.1 MB 391.1 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8xrpMC ![]() 8yi7C M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
---|---|
類似構造データ | 類似検索 - 機能・相同性 ![]() |
-
リンク
EMDBのページ | ![]() ![]() |
---|---|
「今月の分子」の関連する項目 |
-
マップ
ファイル | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | It is a density map generated in C1 symmetry. The central region has a resolution close to 3 angstrom, while the peripheral region exhibited weaker density with low resolution. | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.8697 Å | ||||||||||||||||||||
密度 |
| ||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-ハーフマップ: map half A
ファイル | emd_38609_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | map_half_A | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: map half B
ファイル | emd_38609_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | map_half_B | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-
試料の構成要素
-全体 : The Cryo-EM structure of IL-12, receptor subunit beta-1 and recep...
全体 | 名称: The Cryo-EM structure of IL-12, receptor subunit beta-1 and receptor subunit beta-2 complex |
---|---|
要素 |
|
-超分子 #1: The Cryo-EM structure of IL-12, receptor subunit beta-1 and recep...
超分子 | 名称: The Cryo-EM structure of IL-12, receptor subunit beta-1 and receptor subunit beta-2 complex タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#4 |
---|---|
由来(天然) | 生物種: ![]() |
分子量 | 理論値: 485 KDa |
-分子 #1: Interleukin-12 subunit alpha
分子 | 名称: Interleukin-12 subunit alpha / タイプ: protein_or_peptide / ID: 1 / 詳細: Interleukin-12 subunit alpha / コピー数: 4 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: ![]() |
分子量 | 理論値: 23.781508 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: LSLARNLPVA TPDPGMFPCL HHSQNLLRAV SNMLQKARQT LEFYPCTSEE IDHEDITKDK TSTVEACLPL ELTKNESCLN SRETSFITN GSCLASRKTS FMMALCLSSI YEDLKMYQVE FKTMNAKLLM DPKRQIFLDQ NMLAVIDELM QALNFNSETV P QKSSLEEP ...文字列: LSLARNLPVA TPDPGMFPCL HHSQNLLRAV SNMLQKARQT LEFYPCTSEE IDHEDITKDK TSTVEACLPL ELTKNESCLN SRETSFITN GSCLASRKTS FMMALCLSSI YEDLKMYQVE FKTMNAKLLM DPKRQIFLDQ NMLAVIDELM QALNFNSETV P QKSSLEEP DFYKTKIKLC ILLHAFRIRA VTIDRVMSYL NASHHHHHH UniProtKB: Interleukin-12 subunit alpha |
-分子 #2: Interleukin-12 subunit beta
分子 | 名称: Interleukin-12 subunit beta / タイプ: protein_or_peptide / ID: 2 / 詳細: Interleukin-12 subunit beta / コピー数: 4 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: ![]() |
分子量 | 理論値: 34.811023 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: AIWELKKDVY VVELDWYPDA PGEMVVLTCD TPEEDGITWT LDQSSEVLGS GKTLTIQVKE FGDAGQYTCH KGGEVLSHSL LLLHKKEDG IWSTDILKDQ KEPKNKTFLR CEAKNYSGRF TCWWLTTIST DLTFSVKSSR GSSDPQGVTC GAATLSAERV R GDNKEYEY ...文字列: AIWELKKDVY VVELDWYPDA PGEMVVLTCD TPEEDGITWT LDQSSEVLGS GKTLTIQVKE FGDAGQYTCH KGGEVLSHSL LLLHKKEDG IWSTDILKDQ KEPKNKTFLR CEAKNYSGRF TCWWLTTIST DLTFSVKSSR GSSDPQGVTC GAATLSAERV R GDNKEYEY SVECQEDSAC PAAEESLPIE VMVDAVHKLK YENYTSSFFI RDIIKPDPPK NLQLKPLKNS RQVEVSWEYP DT WSTPHSY FSLTFCVQVQ GKSKREKKDR VFTDKTSATV ICRKNASISV RAQDRYYSSS WSEWASVPCS UniProtKB: Interleukin-12 subunit beta |
-分子 #3: Interleukin-12 receptor subunit beta-2
分子 | 名称: Interleukin-12 receptor subunit beta-2 / タイプ: protein_or_peptide / ID: 3 / 詳細: Interleukin-12 receptor subunit beta-2 / コピー数: 4 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: ![]() |
分子量 | 理論値: 34.627477 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: KIDACKRGDV TVKPSHVILL GSTVNITCSL KPRQGCFHYS RRNKLILYKF DRRINFHHGH SLNSQVTGLP LGTTLFVCKL ACINSDEIQ ICGAEIFVGV APEQPQNLSC IQKGEQGTVA CTWERGRDTH LYTEYTLQLS GPKNLTWQKQ CKDIYCDYLD F GINLTPES ...文字列: KIDACKRGDV TVKPSHVILL GSTVNITCSL KPRQGCFHYS RRNKLILYKF DRRINFHHGH SLNSQVTGLP LGTTLFVCKL ACINSDEIQ ICGAEIFVGV APEQPQNLSC IQKGEQGTVA CTWERGRDTH LYTEYTLQLS GPKNLTWQKQ CKDIYCDYLD F GINLTPES PESNFTAKVT AVNSLGSSSS LPSTFTFLDI VRPLPPWDIR IKFQKASVSR CTLYWRDEGL VLLNRLRYRP SN SRLWNMV NVTKAKGRHD LLDLKPFTEY EFQISSKLHL YKGSWSDWSE SLRAQTPEEH HHHHH UniProtKB: Interleukin-12 receptor subunit beta-2 |
-分子 #4: Interleukin-12 receptor subunit beta-1
分子 | 名称: Interleukin-12 receptor subunit beta-1 / タイプ: protein_or_peptide / ID: 4 / 詳細: Interleukin-12 receptor subunit beta-1 / コピー数: 4 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: ![]() |
分子量 | 理論値: 24.736449 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: CRTSECCFQD PPYPDADSGS ASGPRDLRCY RISSDRYECS WQYEGPTAGV SHFLRCCLSS GRCCYFAAGS ATRLQFSDQA GVSVLYTVT LWVESWARNQ TEKSPEVTLQ LYNSVKYEPP LGDIKVSKLA GQLRMEWETP DNQVGAEVQF RHRTPSSPWK L GDCGPQDD ...文字列: CRTSECCFQD PPYPDADSGS ASGPRDLRCY RISSDRYECS WQYEGPTAGV SHFLRCCLSS GRCCYFAAGS ATRLQFSDQA GVSVLYTVT LWVESWARNQ TEKSPEVTLQ LYNSVKYEPP LGDIKVSKLA GQLRMEWETP DNQVGAEVQF RHRTPSSPWK L GDCGPQDD DTESCLCPLE MNVAQEFQLR RRQLGSQGSS WSKWSSPVCV PPENPHHHHH H UniProtKB: Interleukin-12 receptor subunit beta-1 |
-分子 #6: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 6 / コピー数: 12 / 式: NAG |
---|---|
分子量 | 理論値: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
![]() | 単粒子再構成法 |
試料の集合状態 | particle |
-
試料調製
濃度 | 1.34 mg/mL | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
緩衝液 | pH: 8 構成要素:
詳細: 25mM Tris-HCl pH 8.0,150mM NaCl | |||||||||
グリッド | モデル: Quantifoil / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: LACEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 120 sec. | |||||||||
凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK IV |
-
電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |