An extended interaction site determines binding between AP180 and AP2 in clathrin mediated endocytosis.

Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE

Original Publication: [London] : Nature Pub. Group

Endocytosis* ; Adaptor Protein Complex 2*/metabolism ; Clathrin*/metabolism ; Protein Binding* ; Monomeric Clathrin Assembly Proteins*/metabolism ; Monomeric Clathrin Assembly Proteins*/genetics; Binding Sites ; Humans ; Animals ; Magnetic Resonance Spectroscopy ; Clathrin-Coated Vesicles/metabolism ; Intrinsically Disordered Proteins/metabolism ; Intrinsically Disordered Proteins/chemistry ; Intrinsically Disordered Proteins/genetics

The early phases of clathrin mediated endocytosis are organized through a highly complex interaction network mediated by clathrin associated sorting proteins (CLASPs) that comprise long intrinsically disordered regions (IDRs). AP180 is a CLASP exclusively expressed in neurons and comprises a long IDR of around 600 residues, whose function remains partially elusive. Using NMR spectroscopy, we discovered an extended and strong interaction site within AP180 with the major adaptor protein AP2, and describe its binding dynamics at atomic resolution. We find that the 70 residue-long site determines the overall interaction between AP180 and AP2 in a dynamic equilibrium between its bound and unbound states, while weaker binding sites contribute to the overall affinity at much higher concentrations of AP2. Our data suggest that this particular interaction site might play a central role in recruitment of adaptors to the clathrin coated pit, whereas more transient and promiscuous interactions allow reshaping of the interaction network until cargo uptake inside a coated vesicle.
(© 2024. The Author(s).)

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802209 EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020); ANR-17-ERC3-0004 Agence Nationale de la Recherche (French National Research Agency); ANR-15-IDEX-02 Agence Nationale de la Recherche (French National Research Agency); ANR-10-INBS-0005- 02 Agence Nationale de la Recherche (French National Research Agency)

0 (Adaptor Protein Complex 2)
0 (Clathrin)
0 (clathrin assembly protein AP180)
0 (Monomeric Clathrin Assembly Proteins)
0 (Intrinsically Disordered Proteins)

Date Created: 20240713 Date Completed: 20240713 Latest Revision: 20240731

20240731

PMC11246429

10.1038/s41467-024-50212-4

39003270