EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	TMPRSS2-mediated coronavirus spike activation and inhibition.
ジャーナル・号・ページ	Nat Struct Mol Biol, Vol. 33, Issue 5, Page 810-823, Year 2026
掲載日	2026年4月28日
著者	Matthew McCallum / James Brett Case / Jack T Brown / Young-Jun Park / Jimin Lee / Emmajay Sutherland / Anupriya Aggarwal / Cecily Gibson / Florian A Lempp / Cameron Stewart / M Alejandra Tortorici / Shilpa Sanapala / Jun Siong Low / Daniel Asarnow / Dana Bohan / Exequiel Dellota / Benjamin Merz / Bhavna Chawla / Swagata Kar / Antonio Lanzavecchia / Federica Sallusto / Nicholas M Riley / Stuart Turville / Lisa Purcell / Michael S Diamond / David Veesler /
PubMed 要旨	The protease TMPRSS2 facilitates coronavirus infections, yet its mechanism of viral glycoprotein recognition remains unclear. Here we show that, following ACE2 engagement of the SARS-CoV-2 spike (S) ...The protease TMPRSS2 facilitates coronavirus infections, yet its mechanism of viral glycoprotein recognition remains unclear. Here we show that, following ACE2 engagement of the SARS-CoV-2 spike (S) inducing the early fusion intermediate conformation (E-FIC), TMPRSS2 cleaves the R815 S' site and promotes fusogenic conformational changes leading to viral entry. We unveil TMPRSS2 recognition of S', identify key residues modulating binding specificity and demonstrate that S' site-directed broadly neutralizing antibodies target E-FIC and inhibit viral entry by blocking TMPRSS2 access. We computationally designed stabilized E-FIC as a vaccine candidate, overcoming the transient nature of this state. We describe a TMPRSS2-directed monoclonal antibody inhibiting several coronaviruses, including SARS-CoV-2 variants and protecting mice against SARS-CoV-2 challenge. These results outline the mechanistic role of TMPRSS2 and S' site-directed antibodies in coronavirus entry.
リンク	Nat Struct Mol Biol / PubMed:42050172 / PubMed Central
手法	EM (単粒子)
解像度	2.7 - 3.8 Å
構造データ	70721 9opq EMDB-70721, PDB-9opq: TMPRSS2 (S441A) bound to the HCoV-NL63 S2'region genetically fused to the HCoV-HKU1 RBD 手法: EM (単粒子) / 解像度: 3.3 Å 70722 9opr EMDB-70722, PDB-9opr: TMPRSS2 S441A in complex with the H1H7 Fab and anti-kappa light chain nanobody 手法: EM (単粒子) / 解像度: 3.2 Å 73656 9yyu EMDB-73656, PDB-9yyu: SARS-CoV-2 spike trimer in the early fusion intermediate conformation bound to the VN01H1 Fab (Fab local refinement) 手法: EM (単粒子) / 解像度: 3.3 Å 73657 9yyv EMDB-73657, PDB-9yyv: SARS-CoV-2 spike trimer in the early fusion intermediate conformation bound to the VN01H1 Fab (S2 local refinement) 手法: EM (単粒子) / 解像度: 3.3 Å 73786 9z3j EMDB-73786, PDB-9z3j: HCoV-NL63 S2' peptide bound to TMPRSS2 S441A (complexed with the H1H7 Fab and an anti-kappa-nanobody) 手法: EM (単粒子) / 解像度: 2.8 Å 73787 9z3k EMDB-73787, PDB-9z3k: SARS-CoV-2 S2 trimer stabilized in the early fusion intermediate conformation by circular permutation and clamping by gp41 (E-FICs-v1) 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-75233: SARS-CoV-2 spike trimer in the early fusion intermediate conformation bound to the VN01H1 Fab (global refinement) 手法: EM (単粒子) / 解像度: 3.8 Å 75694 11hk EMDB-75694, PDB-11hk: SARS-CoV-2 spike S2 trimer stabilized in the early fusion intermediate conformation (E-FICs-v3) bound to the VN01H1 Fab (Fab local refinement) 手法: EM (単粒子) / 解像度: 2.7 Å 75695 11hl EMDB-75695, PDB-11hl: SARS-CoV-2 spike S2 trimer stabilized in the early fusion intermediate conformation (E-FICs-v3) bound to the VN01H1 Fab (S2 local refinement) 手法: EM (単粒子) / 解像度: 2.8 Å 75697 11hn EMDB-75697, PDB-11hn: SARS-CoV-2 spike S2 trimer stabilized in the early fusion intermediate conformation (E-FICs-v3) bound to C77G12 (S2 local refinement) 手法: EM (単粒子) / 解像度: 2.7 Å 75705 11hw EMDB-75705, PDB-11hw: SARS-CoV-2 spike S2 trimer stabilized in the early fusion intermediate conformation (E-FICs-v3) bound to C77G12 (Fab local refinement) 手法: EM (単粒子) / 解像度: 2.8 Å EMDB-75721: SARS-CoV-2 spike S2 trimer stabilized in the early fusion intermediate conformation (E-FICs-v3) bound to the VN01H1 Fab 手法: EM (単粒子) / 解像度: 2.9 Å EMDB-75722: SARS-CoV-2 spike S2 trimer stabilized in the early fusion intermediate conformation (E-FICs-v3) bound to C77G12 (global refinement) 手法: EM (単粒子) / 解像度: 2.9 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-HOH: WATER
由来	homo sapiens (ヒト) human coronavirus hku1 (ウイルス) lama glama (ラマ) severe acute respiratory syndrome coronavirus 2 (ウイルス) human coronavirus nl63 (ウイルス) SARS-CoV-2 pseudovirus (ウイルス) saccharomyces cerevisiae s288c (パン酵母)
キーワード	VIRAL PROTEIN / S2prime / coronavirus / SARS-CoV-2 / spike / fusion / entry / antiviral / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN-HYDROLASE complex / VN01H1 / C77G12 / VIRAL PROTEIN complex / VIRAL PROTEIN/HYDROLASE / TMPRSS2 / NL63 / HKU1 / RBD / cleavage / protease / HYDROLASE/IMMUNE SYSTEM / H1H7 / nanobody / antibody / HYDROLASE-IMMUNE SYSTEM complex / VIRAL PROTEIN/IMMUNE SYSTEM / Virus / coronaviruses / E-FIC / ACE2 / Glycoprotein / Receptor / VIRAL PROTEIN-IMMUNE SYSTEM complex