PDBsum entry 6d8c

Structural protein

PDB id: 6d8c

Contents

Protein chains

121 a.a.

370 a.a.

Ligands

HYP-ALA-TRP-G5G-ALA-ALO-CYS ×3

ADP ×5

Metals

_MG ×5

PDB id:

6d8c

Name:

Structural protein

Title:

Cryo-em structure of flnaabd e254k bound to phalloidin-stabilized f- actin

Structure:

Filamin-a. Chain: d, a, b, c, e. Fragment: unp residues 1-278. Synonym: fln-a, actin-binding protein 280, abp-280, alpha-filamin, endothelial actin-binding protein, filamin-1, non-muscle filamin. Engineered: yes. Mutation: yes. Actin, alpha skeletal muscle. Chain: h, j, k, l, m.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: flna, fln, fln1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gallus gallus. Chicken. Organism_taxid: 9031.

Authors:

D.V.Iwamoto,A.R.Huehn,B.Simon,C.Huet-Calderwood,M.Baldassarre, C.V.Sindelar,D.A.Calderwood

Key ref:

D.V.Iwamoto et al. (2018). Structural basis of the filamin A actin-binding domain interaction with F-actin. Nat Struct Mol Biol, 25, 918-927. PubMed id: 30224736 DOI: 10.1038/s41594-018-0128-3

Date:

26-Apr-18 Release date: 19-Sep-18

Protein chains

P21333  (FLNA_HUMAN) -  Filamin-A from Homo sapiens

Seq: 2647 a.a.

Struc: 121 a.a.

Protein chains

P68139  (ACTS_CHICK) -  Actin, alpha skeletal muscle from Gallus gallus

Seq: 377 a.a.

Struc: 370 a.a.

Enzyme reactions

• Enzyme class: Chains H, J, K, L, M: E.C.3.6.4.- - ?????

DOI no: 10.1038/s41594-018-0128-3

Nat Struct Mol Biol 25:918-927 (2018)

PubMed id: 30224736

Structural basis of the filamin A actin-binding domain interaction with F-actin.

D.V.Iwamoto, A.Huehn, B.Simon, C.Huet-Calderwood, M.Baldassarre, C.V.Sindelar, D.A.Calderwood.

ABSTRACT

Actin-cross-linking proteins assemble actin filaments into higher-order structures essential for orchestrating cell shape, adhesion, and motility. Missense mutations in the tandem calponin homology domains of their actin-binding domains (ABDs) underlie numerous genetic diseases, but a molecular understanding of these pathologies is hampered by the lack of high-resolution structures of any actin-cross-linking protein bound to F-actin. Here, taking advantage of a high-affinity, disease-associated mutant of the human filamin A (FLNa) ABD, we combine cryo-electron microscopy and functional studies to reveal at near-atomic resolution how the first calponin homology domain (CH1) and residues immediately N-terminal to it engage actin. We further show that reorientation of CH2 relative to CH1 is required to avoid clashes with actin and to expose F-actin-binding residues on CH1. Our data explain localization of disease-associated loss-of-function mutations to FLNaCH1 and gain-of-function mutations to the regulatory FLNaCH2. Sequence conservation argues that this provides a general model for ABD-F-actin binding.