摘要 : Endosomal sorting complexes required for transport (ESCRT) recognize ubiquitinated cargo and catalyze diverse budding processes including multivesicular body biogenesis, enveloped virus egress, and cytokinesis. We present the crys... 展开 Endosomal sorting complexes required for transport (ESCRT) recognize ubiquitinated cargo and catalyze diverse budding processes including multivesicular body biogenesis, enveloped virus egress, and cytokinesis. We present the crystal structure of an N-terminal fragment of the deubiquitinating enzyme AMSH (AMSHDC) in complex with the C-terminal region of ESCRT-III CHMP3 (CHMP3DN). AMSHDC folds into an elongated 90 A° long helical assembly that includes an unusual MIT domain. CHMP3DN is unstructured in solution and helical in complex with AMSHDC, revealing a novel MIT domain interacting motif (MIM) that does not overlap with the CHMP1- AMSH binding site. ITC and SPR measurements demonstrate an unusual high-affinity MIM-MIT interaction. Structural analysis suggests a regulatory role for the N-terminal helical segment of AMSHDC and its destabilization leads to a loss of function during HIV-1 budding. Our results indicate a tight coupling of ESCRT-III CHMP3 and AMSH functions and provide insight into the regulation of ESCRT-III. 收起