Structure of the ESCRT-II endosomal trafficking complex

Area of Science:

• Cell Biology
• Molecular Biology
• Structural Biology

Background:

• The multivesicular-body (MVB) pathway is essential for endosomal sorting of transmembrane proteins and lipids.
• This pathway plays critical roles in receptor downregulation, signaling, immune response, and viral budding.
• Ubiquitination signals cargo for sorting into the MVB pathway via ESCRT-I, -II, and -III complexes.

Purpose of the Study:

• To determine the crystal structure of the core yeast ESCRT-II complex.
• To understand the structural basis for cargo recognition and transfer within the MVB pathway.

Main Methods:

• X-ray crystallography was used to determine the structure of the yeast ESCRT-II core complex.
• Structural analysis focused on the arrangement of Vps22, Vps36, and Vps25 proteins.

Main Results:

• The core yeast ESCRT-II complex adopts a 'Y' shape.
• Specific domains of Vps22 and Vps36, including the ubiquitin-binding NZF domain, protrude from the complex.
• Vps22 and Vps36 interact with Vps25 molecules at the center of the 'Y' structure.

Conclusions:

• The determined structure provides insights into the mechanism of ubiquitinated cargo transfer between ESCRT components.
• This structural understanding facilitates further investigation into the MVB pathway's function in protein sorting.