PDBsum entry 6uby

Structural protein

PDB id: 6uby

Contents

Protein chains

(+ 0 more) 370 a.a.

190 a.a.

166 a.a.

164 a.a.

Ligands

ADP ×7

Metals

_MG ×7

PDB id:

6uby

Name:

Structural protein

Title:

Isolated cofilin bound to an actin filament

Structure:

Actin, alpha skeletal muscle. Chain: a, b, c, d, e, f, g, h. Synonym: alpha-actin-1. Cofilin-1. Chain: i. Synonym: 18 kda phosphoprotein,p18,cofilin,non-muscle isoform. Engineered: yes

Source:

Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986. Homo sapiens. Human. Organism_taxid: 9606. Gene: cfl1, cfl. Expressed in: escherichia coli. Expression_system_taxid: 562

Authors:

A.R.Huehn,J.P.Bibeau,A.C.Schramm,W.Cao,E.M.De La Cruz,C.V.Sindelar

Key ref:

A.R.Huehn et al. (2020). Structures of cofilin-induced structural changes reveal local and asymmetric perturbations of actin filaments. Proc Natl Acad Sci U S A, 117, 1478-1484. PubMed id: 31900364 DOI: 10.1073/pnas.1915987117

Date:

13-Sep-19 Release date: 01-Jan-20

Protein chains

P68135  (ACTS_RABIT) -  Actin, alpha skeletal muscle from Oryctolagus cuniculus

Seq: 377 a.a.

Struc: 370 a.a.

Protein chain

P68135  (ACTS_RABIT) -  Actin, alpha skeletal muscle from Oryctolagus cuniculus

Seq: 377 a.a.

Struc: 190 a.a.

Protein chain

P68135  (ACTS_RABIT) -  Actin, alpha skeletal muscle from Oryctolagus cuniculus

Seq: 377 a.a.

Struc: 166 a.a.*

Protein chain

P23528  (COF1_HUMAN) -  Cofilin-1 from Homo sapiens

Seq: 166 a.a.

Struc: 164 a.a.

* PDB and UniProt seqs differ at 37 residue positions (black crosses)

Enzyme reactions

• Enzyme class 2: Chains A, B, C, D, E, F, G, H: E.C.3.6.4.- - ?????
• Enzyme class 3: Chain I: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

DOI no: 10.1073/pnas.1915987117

Proc Natl Acad Sci U S A 117:1478-1484 (2020)

PubMed id: 31900364

Structures of cofilin-induced structural changes reveal local and asymmetric perturbations of actin filaments.

A.R.Huehn, J.P.Bibeau, A.C.Schramm, W.Cao, E.M.De La Cruz, C.V.Sindelar.

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.