Abstract
Clathrin-mediated endocytosis is a process by which specific molecules are internalized from the cell periphery for delivery to early endosomes. The key stages in this step-wise process, from the starting point of cargo recognition, to the later stage of assembly of the clathrin coat, are dependent on weak interactions between a large network of proteins. This review discusses the structural and functional data that have improved our knowledge and understanding of the main weak molecular interactions implicated in clathrin-mediated endocytosis, with a particular focus on the two key proteins: AP2 and clathrin.
Highlights
Biological processes are built on a complex interplay between proteins in the crowded, heterogeneous environment that exists within cells; and the functional protein interactions that are vital to these processes are often weak and transient
Schmid et al (2006) proposed that clathrin coated pit (CCP) formation proceeds as a result of high avidity interactions of accessory proteins being replaced by the weak interactions of the clathrin coat with adaptors; meaning that initially low affinity interactions between cargo and adaptors, between adaptors and accessory proteins, and between accessory proteins and clathrin, are used to build the network
This review of the structural and functional experiments that investigated the binding between cargo, adaptor and accessory proteins, as well as clathrin, has demonstrated the different ways weak molecular interactions are exploited in clathrin-mediated endocytosis
Summary
Biological processes are built on a complex interplay between proteins in the crowded, heterogeneous environment that exists within cells; and the functional protein interactions that are vital to these processes are often weak and transient. Phe259 of the ARH peptide fitted into an adjacent, complementary hydrophobic pocket on the β2-appendage which the authors denote the “[F] pocket,” and the side chain of the residue Arg266 extends along a small channel on the surface of the β2 subdomain ([R] pocket) which forms hydrogen bonds with acidic residues Glu902 and Glu849 For these F, [FL] and [R] pocket interactions to occur, the α-helical motif must fit into its binding groove, providing the specificity for binding. Further analysis showed that epsin, ARH and β-arrestin contain acidic residues N-terminal to the proximal phenylalanine and the β2-appendage binding motif is more accurately described as: [DE]nX1–2FXX[FL]XXXR Taken together, these data reveal fundamental differences in the mode of interaction between the β2 platform domain and CLASPs compared to other appendage-ligand interactions. Schmid et al (2006) proposed that clathrin coated pit (CCP) formation proceeds as a result of high avidity interactions of accessory proteins being replaced by the weak interactions of the clathrin coat with adaptors; meaning that initially low affinity (and readily reversible) interactions between cargo and adaptors, between adaptors and accessory proteins, and between accessory proteins and clathrin, are used to build the network
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