EMD-39569

Single-particle
3.2 Å
EMD-39569 Deposition: 25/03/2024
Map released: 11/12/2024
Last modified: 25/12/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-39569

Cryo-EM structure of the dystrophin glycoprotein complex

EMD-39569

Single-particle
3.2 Å
EMD-39569 Deposition: 25/03/2024
Map released: 11/12/2024
Last modified: 25/12/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Mus musculus
Sample: dystrophin glycoprotein complex, DGC

Deposition Authors: Wu JP , Yan Z , Wan L
Structure and assembly of the dystrophin glycoprotein complex.
Wan L , Ge X , Xu Q, Huang G, Yang T, Campbell KP , Yan Z , Wu J
(2024) Nature
PUBMED: 39663450
DOI: doi:10.1038/s41586-024-08310-2
ISSN: 1476-4687
ASTM: NATUAS
Abstract:
The dystrophin glycoprotein complex (DGC) has a crucial role in maintaining cell membrane stability and integrity by connecting the intracellular cytoskeleton with the surrounding extracellular matrix1-3. Dysfunction of dystrophin and its associated proteins results in muscular dystrophy, a disorder characterized by progressive muscle weakness and degeneration4,5. Despite the important roles of the DGC in physiology and pathology, its structural details remain largely unknown, hindering a comprehensive understanding of its assembly and function. Here we isolated the native DGC from mouse skeletal muscle and obtained its high-resolution structure. Our findings unveil a markedly divergent structure from the previous model of DGC assembly. Specifically, on the extracellular side, β-, γ- and δ-sarcoglycans co-fold to form a specialized, extracellular tower-like structure, which has a central role in complex assembly by providing binding sites for α-sarcoglycan and dystroglycan. In the transmembrane region, sarcoglycans and sarcospan flank and stabilize the single transmembrane helix of dystroglycan, rather than forming a subcomplex as previously proposed6-8. On the intracellular side, sarcoglycans and dystroglycan engage in assembly with the dystrophin-dystrobrevin subcomplex through extensive interaction with the ZZ domain of dystrophin. Collectively, these findings enhance our understanding of the structural linkage across the cell membrane and provide a foundation for the molecular interpretation of many muscular dystrophy-related mutations.