title: Peptide-in-groove interactions link target proteins to the beta-propeller of clathrin.
abstract: The "WD40" domain is a widespread recognition module for linking partner proteins in intracellular networks of signaling and sorting. The clathrin amino-terminal domain, which directs incorporation of cargo into coated pits, is a beta-propeller closely related in structure to WD40 modules. The crystallographically determined structures of complexes of the clathrin-terminal domain with peptides derived from two different cargo adaptors, beta-arrestin 2 and the beta-subunit of the AP-3 complex, reveal strikingly similar peptide-in-groove interactions. The two peptides in our structures contain related, five-residue motifs, which form the core of their contact with clathrin. A number of other proteins involved in endocytosis have similar "clathrin-box" motifs, and it therefore is likely that they all bind the terminal domain in the same way. We propose that a peptide-in-groove interaction is an important general mode by which beta-propellers recognize specific target proteins.
authors.affiliation: Howard Hughes Medical Institute and Children's Hospital, Laboratory of Molecular Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: E
authors.initials: E
authors.lastname: ter Haar
authors.forename: S C
authors.initials: SC
authors.lastname: Harrison
authors.forename: T
authors.initials: T
authors.lastname: Kirchhausen
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D019390:Arrestins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D002966:Clathrin / Q000737:chemistry* / Q000378:metabolism; D016384:Consensus Sequence; D018360:Crystallography, X-Ray; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid; D000071557:beta-Arrestins
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D019390:Arrestins; D002966:Clathrin; D046911:Macromolecular Substances; D034041:Monomeric Clathrin Assembly Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010750:Phosphoproteins; D000071557:beta-Arrestins; C439023:clathrin assembly protein AP180