National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01 GM127548-01A1
米国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2022 タイトル: Structural basis of an endocytic checkpoint that primes the AP2 clathrin adaptor for cargo internalization. 著者: Edward A Partlow / Kevin S Cannon / Gunther Hollopeter / Richard W Baker / 要旨: Clathrin-mediated endocytosis (CME) is the main route of internalization from the plasma membrane. It is known that the heterotetrameric AP2 clathrin adaptor must open to simultaneously engage ...Clathrin-mediated endocytosis (CME) is the main route of internalization from the plasma membrane. It is known that the heterotetrameric AP2 clathrin adaptor must open to simultaneously engage membrane and endocytic cargo, yet it is unclear how transmembrane cargos are captured to catalyze CME. Using cryogenic-electron microscopy, we discover a new way in which mouse AP2 can reorganize to expose membrane- and cargo-binding pockets, which is not observed in clathrin-coated structures. Instead, it is stimulated by endocytic pioneer proteins called muniscins, which do not enter vesicles. Muniscin-engaged AP2 is primed to rearrange into the vesicle-competent conformation on binding the tyrosine cargo internalization motif (YxxΦ). We propose adaptor priming as a checkpoint to ensure cargo internalization.
全体 : AP2 complex bound to heparin in the "bowl" conformation
全体
名称: AP2 complex bound to heparin in the "bowl" conformation
要素
複合体: AP2 complex bound to heparin in the "bowl" conformation
タンパク質・ペプチド: AP-2 complex subunit alpha-2
タンパク質・ペプチド: AP-2 complex subunit beta
タンパク質・ペプチド: AP-2 complex subunit mu
タンパク質・ペプチド: AP-2 complex subunit sigma
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超分子 #1: AP2 complex bound to heparin in the "bowl" conformation
超分子
名称: AP2 complex bound to heparin in the "bowl" conformation タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all
由来(天然)
生物種: Mus musculus (ハツカネズミ)
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分子 #1: AP-2 complex subunit alpha-2
分子
名称: AP-2 complex subunit alpha-2 / タイプ: protein_or_peptide / ID: 1 詳細: Expressed as a C-terminal GST fusion and the tag was removed with Prescission protease コピー数: 1 / 光学異性体: LEVO