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	A structure-based mechanism for initiation of AP-3 coated vesicle formation.
ジャーナル・号・ページ	Proc Natl Acad Sci U S A, Vol. 121, Issue 52, Page e2411974121, Year 2024
掲載日	2024年12月24日
著者	Matthew Begley / Mahira Aragon / Richard W Baker /
PubMed 要旨	Adaptor protein complex-3 (AP-3) mediates cargo sorting from endosomes to lysosomes and lysosome-related organelles. Recently, it was shown that AP-3 adopts a constitutively open conformation ...Adaptor protein complex-3 (AP-3) mediates cargo sorting from endosomes to lysosomes and lysosome-related organelles. Recently, it was shown that AP-3 adopts a constitutively open conformation compared to the related AP-1 and AP-2 coat complexes, which are inactive until undergoing large conformational changes upon membrane recruitment. How AP-3 is regulated is therefore an open question. To understand the mechanism of AP-3 membrane recruitment and activation, we reconstituted human AP-3 and determined multiple structures in the soluble and membrane-bound states using electron cryo-microscopy. Similar to yeast AP-3, human AP-3 is in a constitutively open conformation. To reconstitute AP-3 activation by adenosine di-phosphate (ADP)-ribosylation factor 1 (Arf1), a small guanosine tri-phosphate (GTP)ase, we used lipid nanodiscs to build Arf1-AP-3 complexes on membranes and determined three structures showing the stepwise conformational changes required for formation of AP-3 coated vesicles. First, membrane recruitment is driven by one of two predicted Arf1 binding sites, which flexibly tethers AP-3 to the membrane. Second, cargo binding causes AP-3 to adopt a fixed position and rigidifies the complex, which stabilizes binding for a second Arf1 molecule. Finally, binding of the second Arf1 molecule provides the template for AP-3 dimerization, providing a glimpse into the first step of coat polymerization. We propose coat polymerization only occurs after cargo engagement, thereby linking cargo sorting with assembly of higher-order coat structures. Additionally, we provide evidence for two amphipathic helices in AP-3, suggesting that AP-3 contributes to membrane deformation during coat assembly. In total, these data provide evidence for the first stages of AP-3-mediated vesicle coat assembly.
リンク	Proc Natl Acad Sci U S A / PubMed:39705307 / PubMed Central
手法	EM (単粒子)
解像度	3.6 - 5.6 Å
構造データ	45207 9c58 EMDB-45207, PDB-9c58: AP-3 bound to myristoylated Arf1 (Q71L) 手法: EM (単粒子) / 解像度: 4.7 Å 45208 9c59 EMDB-45208, PDB-9c59: Human AP-3 dimer bound to myristoylated Arf1 (Q71L) and LAMP1 cargo on a lipid nanodisc 手法: EM (単粒子) / 解像度: 4.3 Å 45209 9c5a EMDB-45209, PDB-9c5a: AP-3 Arf1 dimeric interface, focused refinement 手法: EM (単粒子) / 解像度: 4.2 Å EMDB-45210: AP-3 bound to myristoylated Arf1 and LAMPI on a lipid nanodisc; concensus refinement 手法: EM (単粒子) / 解像度: 4.2 Å EMDB-45211: AP-3 bound to myristoylated Arf1 and LAMPI on a lipid nanodisc; focus refinement 1 手法: EM (単粒子) / 解像度: 4.5 Å EMDB-45212: AP-3 bound to myristoylated Arf1 and LAMPI on a lipid nanodisc; focus refinement 2 手法: EM (単粒子) / 解像度: 5.6 Å 45213 9c5b EMDB-45213, PDB-9c5b: AP-3 bound to myristoylated Arf1 (Q71L) and LAMPI on a lipid nanodisc; combined map 手法: EM (単粒子) / 解像度: 4.5 Å 45214 9c5c EMDB-45214, PDB-9c5c: Structure of Human Adaptor Protein Complex AP-3 in the Apo State 手法: EM (単粒子) / 解像度: 3.6 Å
化合物	ChemComp-MG: Unknown entry ChemComp-GTP: GUANOSINE-5'-TRIPHOSPHATE / GTP, エネルギー貯蔵分子*YM
由来	homo sapiens (ヒト)
キーワード	TRANSPORT PROTEIN / Adaptor Protein complex / AP-3 / Lysosomal transport / Endosomal transport / Protein trafficking / Endosomal Trafficking / Lysosomal Trafficking / Protein transport / AP complex