7AQZ

Co-Crystal Structure of Variant Surface Glycoprotein VSG2 in complex with Nanobody VSG2(NB14)

7AQZ の概要

• エントリーDOI: 10.2210/pdb7aqz/pdb
• 分子名称: Variant surface glycoprotein MITAT 1.2, Nanobody VSG2(NB14), alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: variant surface glycoprotein, epitope mapping, immune evasion, membrane protein
• 由来する生物種: Lama glama (Llama); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 108534.53

構造登録者

Stebbins, C.E.,Hempelmann, A.,VanStraaten, M. (登録日: 2020-10-23, 公開日: 2021-11-03, 最終更新日: 2024-11-13)

主引用文献

Hempelmann, A.,Hartleb, L.,van Straaten, M.,Hashemi, H.,Zeelen, J.P.,Bongers, K.,Papavasiliou, F.N.,Engstler, M.,Stebbins, C.E.,Jones, N.G.
Nanobody-mediated macromolecular crowding induces membrane fission and remodeling in the African trypanosome.
Cell Rep, 37:109923-109923, 2021

PubMed Abstract: The dense variant surface glycoprotein (VSG) coat of African trypanosomes represents the primary host-pathogen interface. Antigenic variation prevents clearing of the pathogen by employing a large repertoire of antigenically distinct VSG genes, thus neutralizing the host's antibody response. To explore the epitope space of VSGs, we generate anti-VSG nanobodies and combine high-resolution structural analysis of VSG-nanobody complexes with binding assays on living cells, revealing that these camelid antibodies bind deeply inside the coat. One nanobody causes rapid loss of cellular motility, possibly due to blockage of VSG mobility on the coat, whose rapid endocytosis and exocytosis are mechanistically linked to Trypanosoma brucei propulsion and whose density is required for survival. Electron microscopy studies demonstrate that this loss of motility is accompanied by rapid formation and shedding of nanovesicles and nanotubes, suggesting that increased protein crowding on the dense membrane can be a driving force for membrane fission in living cells.

PubMed: 34731611
DOI: 10.1016/j.celrep.2021.109923

実験手法

X-RAY DIFFRACTION (1.3 Å)