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-Structure paper
タイトル | Structure of the HOPS tethering complex, a lysosomal membrane fusion machinery. |
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ジャーナル・号・ページ | Elife, Vol. 11, Year 2022 |
掲載日 | 2022年9月13日 |
著者 | Dmitry Shvarev / Jannis Schoppe / Caroline König / Angela Perz / Nadia Füllbrunn / Stephan Kiontke / Lars Langemeyer / Dovile Januliene / Kilian Schnelle / Daniel Kümmel / Florian Fröhlich / Arne Moeller / Christian Ungermann / |
PubMed 要旨 | Lysosomes are essential for cellular recycling, nutrient signaling, autophagy, and pathogenic bacteria and viruses invasion. Lysosomal fusion is fundamental to cell survival and requires HOPS, a ...Lysosomes are essential for cellular recycling, nutrient signaling, autophagy, and pathogenic bacteria and viruses invasion. Lysosomal fusion is fundamental to cell survival and requires HOPS, a conserved heterohexameric tethering complex. On the membranes to be fused, HOPS binds small membrane-associated GTPases and assembles SNAREs for fusion, but how the complex fulfills its function remained speculative. Here, we used cryo-electron microscopy to reveal the structure of HOPS. Unlike previously reported, significant flexibility of HOPS is confined to its extremities, where GTPase binding occurs. The SNARE-binding module is firmly attached to the core, therefore, ideally positioned between the membranes to catalyze fusion. Our data suggest a model for how HOPS fulfills its dual functionality of tethering and fusion and indicate why it is an essential part of the membrane fusion machinery. |
リンク | Elife / PubMed:36098503 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.89 - 5.0 Å |
構造データ | EMDB-14964: HOPS tethering complex from yeast, composite map EMDB-14965: HOPS tethering complex from yeast, consensus map covering the upper part of the complex EMDB-14966: HOPS tethering complex from yeast, consensus map covering the bottom part of the complex EMDB-14967: HOPS tethering complex from yeast, local refinement map of the SNARE-binding module EMDB-14968: HOPS tethering complex from yeast, local refinement map of the backbone part of the complex EMDB-14969: HOPS tethering complex from yeast, local refinement map of the bottom part of the complex (Vps18) EMDB-14970: HOPS tethering complex from yeast, local refinement map of the bottom part of the complex (Vps39) PDB-7zty: |
化合物 | ChemComp-HOH: |
由来 |
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キーワード | TRANSPORT PROTEIN / tethering / membrane fusion / GTPase effector / HOPS / CYTOSOLIC PROTEIN / tethering complex / lysosome / Rab GTPase / cryo-EM |