6UC4

Barbed end side of a cofilactin cluster

Summary for 6UC4

• Entry DOI: 10.2210/pdb6uc4/pdb
• Related: 6UBY 6UC0
• EMDB information: 20711 20719 20721 20724 20726
• Descriptor: Actin, alpha skeletal muscle, Cofilin-1, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: cytoskeleton, structural protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 16
• Total formula weight: 559792.69

Authors

Huehn, A.R.,Bibeau, J.P.,Schramm, A.C.,Cao, W.,De La Cruz, E.M.,Sindelar, C.V. (deposition date: 2019-09-13, release date: 2020-01-01, Last modification date: 2024-03-20)

Primary citation

Huehn, A.R.,Bibeau, J.P.,Schramm, A.C.,Cao, W.,De La Cruz, E.M.,Sindelar, C.V.
Structures of cofilin-induced structural changes reveal local and asymmetric perturbations of actin filaments.
Proc.Natl.Acad.Sci.USA, 117:1478-1484, 2020

PubMed Abstract: Members of the cofilin/ADF family of proteins sever actin filaments, increasing the number of filament ends available for polymerization or depolymerization. Cofilin binds actin filaments with positive cooperativity, forming clusters of contiguously bound cofilin along the filament lattice. Filament severing occurs preferentially at boundaries between bare and cofilin-decorated (cofilactin) segments and is biased at 1 side of a cluster. A molecular understanding of cooperative binding and filament severing has been impeded by a lack of structural data describing boundaries. Here, we apply methods for analyzing filament cryo-electron microscopy (cryo-EM) data at the single subunit level to directly investigate the structure of boundaries within partially decorated cofilactin filaments. Subnanometer resolution maps of isolated, bound cofilin molecules and an actin-cofilactin boundary indicate that cofilin-induced actin conformational changes are local and limited to subunits directly contacting bound cofilin. An isolated, bound cofilin compromises longitudinal filament contacts of 1 protofilament, consistent with a single cofilin having filament-severing activity. An individual, bound phosphomimetic (S3D) cofilin with weak severing activity adopts a unique binding mode that does not perturb actin structure. Cofilin clusters disrupt both protofilaments, consistent with a higher severing activity at boundaries compared to single cofilin. Comparison of these structures indicates that this disruption is substantially greater at pointed end sides of cofilactin clusters than at the barbed end. These structures, with the distribution of bound cofilin clusters, suggest that maximum binding cooperativity is achieved when 2 cofilins occupy adjacent sites. These results reveal the structural origins of cooperative cofilin binding and actin filament severing.

PubMed: 31900364
DOI: 10.1073/pnas.1915987117

Experimental method

ELECTRON MICROSCOPY (9.2 Å)