Interaction of two structurally distinct sequence types with the clathrin terminal domain beta-propeller

The amino-terminal domain of the clathrin heavy chain, which folds into a s even-bladed P-propeller, binds directly to several endocytic proteins via s hort sequences based on the consensus residues LLDLD. In addition to a sing le LLDLD-based, type I clathrin-binding sequence, both amphiphysin and epsi n contain a second, distinct sequence that is also capable of binding to cl athrin directly. Here, we analyzed these sequences, which we term type II s equences, and show that the (257)LMDLA sequence in rat epsin 1 appears to b e a weak clathrin-binding variant of the sequence (PWDLW)-P-417 originally found in human amphiphysin Il. The structural features of the type II seque nce required for association with clathrin are distinct from the LLDLD-base d sequence. In the central segment of amphiphysin, the type I and type II s equences cooperate to effect optimal clathrin binding and the formation of sedimentable assemblies. Together, the data provide evidence for two intera ction surfaces upon certain endocytic accessory proteins that could coopera te with other coat components to enhance clathrin bud formation at the cell surface.