2XZE

Structural basis for AMSH-ESCRT-III CHMP3 interaction

Summary for 2XZE

• Entry DOI: 10.2210/pdb2xze/pdb
• Related: 2GD5
• Descriptor: STAM-BINDING PROTEIN, CHARGED MULTIVESICULAR BODY PROTEIN 3 (3 entities in total)
• Functional Keywords: hydrolase-protein transport complex, hydrolase/protein transport
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Nucleus: O95630; Cytoplasm, cytosol: Q9Y3E7
• Total number of polymer chains: 4
• Total formula weight: 42988.57

Authors

Solomons, J.,Sabin, C.,Weissenhorn, W. (deposition date: 2010-11-25, release date: 2011-08-24, Last modification date: 2024-05-08)

Primary citation

Solomons, J.,Sabin, C.,Poudevigne, E.,Usami, Y.,Hulsik, D.L.,Macheboeuf, P.,Hartlieb, B.,Gottlinger, H.,Weissenhorn, W.
Structural Basis for Escrt-III Chmp3 Recruitment of Amsh.
Structure, 19:1149-, 2011

PubMed Abstract: 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 (AMSHΔC) in complex with the C-terminal region of ESCRT-III CHMP3 (CHMP3ΔN). AMSHΔC folds into an elongated 90 Å long helical assembly that includes an unusual MIT domain. CHMP3ΔN is unstructured in solution and helical in complex with AMSHΔC, 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 AMSHΔC 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.

PubMed: 21827950
DOI: 10.1016/J.STR.2011.05.011

Experimental method

X-RAY DIFFRACTION (1.75 Å)