ジャーナル: Nat Commun / 年: 2025 タイトル: Spatial N-glycan rearrangement on αβ integrin nucleates galectin-3 oligomers to determine endocytic fate. 著者: Massiullah Shafaq-Zadah / Estelle Dransart / Ilyes Hamitouche / Christian Wunder / Valérie Chambon / Cesar A Valades-Cruz / Ludovic Leconte / Nirod Kumar Sarangi / Jack Robinson / Siau-Kun ...著者: Massiullah Shafaq-Zadah / Estelle Dransart / Ilyes Hamitouche / Christian Wunder / Valérie Chambon / Cesar A Valades-Cruz / Ludovic Leconte / Nirod Kumar Sarangi / Jack Robinson / Siau-Kun Bai / Raju Regmi / Aurélie Di Cicco / Agnès Hovasse / Richard Bartels / Ulf J Nilsson / Sarah Cianférani-Sanglier / Hakon Leffler / Tia E Keyes / Daniel Lévy / Stefan Raunser / Daniel Roderer / Ludger Johannes / 要旨: Membrane glycoproteins frequently adopt different conformations when altering between active and inactive states. Here, we discover a molecular switch that exploits dynamic spatial rearrangements of ...Membrane glycoproteins frequently adopt different conformations when altering between active and inactive states. Here, we discover a molecular switch that exploits dynamic spatial rearrangements of N-glycans during such conformational transitions to control protein function. For the conformationally switchable cell adhesion glycoprotein αβ integrin, we find that only the bent-closed state arranges N-glycans to nucleate the formation of up to tetrameric oligomers of the glycan-binding protein galectin-3. We propose a structural model of how these galectin-3 oligomers are built and how they clamp the bent-closed state to select it for endocytic uptake and subsequent retrograde trafficking to the Golgi for polarized distribution in cells. Our findings reveal the dynamic regulation of the glycan landscape at the cell surface to achieve oligomerization of galectin-3. Galectin-3 oligomers are thereby identified as functional decoders of defined spatial patterns of N-glycans on specifically the bent-closed conformational state of αβ integrin and possibly other integrin family members.
凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 285 K / 装置: FEI VITROBOT MARK IV / 詳細: blot force -1, blotting time 3.5 sec.
詳細
Peptidisc-embedded protein complex. Vitrification immediately after elution from NiNTA beads to minimize dissociation.
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電子顕微鏡法
顕微鏡
TFS KRIOS
特殊光学系
球面収差補正装置: No Cs corrector / 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
撮影
フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 2 / 実像数: 16353 / 平均露光時間: 3.0 sec. / 平均電子線量: 61.0 e/Å2 詳細: Two data sets with 6028 and 10325 images recorded under identical conditions