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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 7oix | ||||||
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タイトル | Structure of thermostable human MFSD2A in complex with thermostable human Sync2 | ||||||
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![]() | MEMBRANE PROTEIN / human membrane protein / MFS transporter / human endogenous retroviral protein / syncytin | ||||||
機能・相同性 | ![]() lysophosphatidylcholine flippase activity / regulation of phosphatidylethanolamine metabolic process / regulation of phosphatidylserine metabolic process / oleate transmembrane transporter activity / regulation of phosphatidylcholine metabolic process / regulation of neuron projection arborization / retina morphogenesis in camera-type eye / fatty acid transmembrane transporter activity / photoreceptor cell morphogenesis / lysophospholipid translocation ...lysophosphatidylcholine flippase activity / regulation of phosphatidylethanolamine metabolic process / regulation of phosphatidylserine metabolic process / oleate transmembrane transporter activity / regulation of phosphatidylcholine metabolic process / regulation of neuron projection arborization / retina morphogenesis in camera-type eye / fatty acid transmembrane transporter activity / photoreceptor cell morphogenesis / lysophospholipid translocation / lysophospholipid:sodium symporter activity / lysophospholipid transport / syncytium formation by plasma membrane fusion / syncytium formation / photoreceptor cell outer segment organization / lipid transport across blood-brain barrier / very-low-density lipoprotein particle assembly / negative regulation of fatty acid beta-oxidation / regulation of dendrite development / retinal pigment epithelium development / phospholipid transporter activity / positive regulation of triglyceride biosynthetic process / phosphatidylcholine biosynthetic process / : / establishment of blood-brain barrier / myoblast fusion / transcytosis / motor behavior / long-chain fatty acid transmembrane transporter activity / maintenance of blood-brain barrier / Synthesis of PC / plasma membrane => GO:0005886 / carbohydrate transport / transport across blood-brain barrier / regulation of multicellular organism growth / fatty acid transport / long-chain fatty acid transport / energy homeostasis / cellular response to starvation / hippocampus development / brain development / cognition / positive regulation of cell growth / membrane => GO:0016020 / endoplasmic reticulum membrane / plasma membrane 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: 3.6 Å | ||||||
![]() | Martinez-Molledo, M. / Reyes, N. | ||||||
資金援助 | European Union, 1件
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![]() | ![]() タイトル: Structural insights into the lysophospholipid brain uptake mechanism and its inhibition by syncytin-2. 著者: Maria Martinez-Molledo / Emmanuel Nji / Nicolas Reyes / ![]() 要旨: Brain development and function require uptake of essential omega-3 fatty acids in the form of lysophosphatidylcholine via major-facilitator superfamily transporter MFSD2A, a potential pharmaceutical ...Brain development and function require uptake of essential omega-3 fatty acids in the form of lysophosphatidylcholine via major-facilitator superfamily transporter MFSD2A, a potential pharmaceutical target to modulate blood-brain barrier (BBB) permeability. MFSD2A is also the receptor of endogenous retroviral envelope syncytin-2 (SYNC2) in human placenta, where it mediates cell-cell fusion and formation of the maternal-fetal interface. Here, we report a cryo-electron microscopy structure of the human MFSD2A-SYNC2 complex that reveals a large hydrophobic cavity in the transporter C-terminal domain to occlude long aliphatic chains. The transporter architecture suggests an alternating-access transport mechanism for lipid substrates in mammalian MFS transporters. SYNC2 establishes an extensive binding interface with MFSD2A, and a SYNC2-soluble fragment acts as a long-sought-after inhibitor of MFSD2A transport. Our work uncovers molecular mechanisms important to brain and placenta development and function, and SYNC2-mediated inhibition of MFSD2A transport suggests strategies to aid delivery of therapeutic macromolecules across the BBB. | ||||||
履歴 |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 145.1 KB | 表示 | ![]() |
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PDB形式 | ![]() | 112.1 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 12935MC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 59613.219 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() | ||
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#2: タンパク質 | 分子量: 58540.805 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 遺伝子: MFSD2A, MFSD2, NLS1, HMFN0656, PP9177, UNQ300/PRO341 発現宿主: ![]() | ||
#3: 多糖 | alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-6)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose タイプ: oligosaccharide / 分子量: 910.823 Da / 分子数: 1 / 由来タイプ: 組換発現 | ||
#4: 多糖 | alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)-alpha-D- ...alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose タイプ: oligosaccharide / 分子量: 1235.105 Da / 分子数: 1 / 由来タイプ: 組換発現 | ||
#5: 糖 | ChemComp-NAG / 研究の焦点であるリガンドがあるか | N | |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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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 |
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試料調製
構成要素 | 名称: Thermostable human MFSD2A in complex with thermostable human Syncytin-2 タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT | ||||||||||||||||||||
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分子量 | 実験値: NO | ||||||||||||||||||||
由来(天然) | 生物種: ![]() | ||||||||||||||||||||
由来(組換発現) | 生物種: ![]() | ||||||||||||||||||||
緩衝液 | pH: 7.4 | ||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 1.2 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||
試料支持 | 詳細: 2 mA / グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 | ||||||||||||||||||||
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 K |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1800 nm / 最小 デフォーカス(公称値): 500 nm / Cs: 2.7 mm / C2レンズ絞り径: 50 µm |
撮影 | 電子線照射量: 47.1 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.17.1_3660: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 1461938 | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 94703 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: AB INITIO MODEL / 空間: REAL | ||||||||||||||||||||||||
精密化 | 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 67.61 Å2 | ||||||||||||||||||||||||
拘束条件 |
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