PDBsum entry 4b7l

Structural protein

PDB id: 4b7l

Contents

Protein chain

328 a.a.

Waters ×421

PDB id:

4b7l

Name:

Structural protein

Title:

Crystal structure of human filamin b actin binding domain with 1st filamin repeat

Structure:

Filamin-b. Chain: a, b. Fragment: actin-binding domain with repeat 1, residues 1-347. Synonym: fln-b, abp-278, abp-280 homolog, actin-binding-like protein, beta-filamin, filamin homolog 1, fh1, filamin-3, thyroid autoantigen, truncated actin-binding protein, truncated abp, actin binding domain with filamin repeat 1. Engineered: yes. Mutation: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.05Å R-factor: 0.185 R-free: 0.219

Authors:

G.M.Sawyer,A.J.Sutherland-Smith

Key ref:

G.M.Sawyer and A.J.Sutherland-Smith (2012). Crystal structure of the filamin N-terminal region reveals a hinge between the actin binding and first repeat domains. J Mol Biol, 424, 240-247. PubMed id: 23036857

Date:

20-Aug-12 Release date: 10-Oct-12

Protein chains

O75369  (FLNB_HUMAN) -  Filamin-B from Homo sapiens

Seq: 2602 a.a.

Struc: 328 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

J Mol Biol 424:240-247 (2012)

PubMed id: 23036857

Crystal structure of the filamin N-terminal region reveals a hinge between the actin binding and first repeat domains.

G.M.Sawyer, A.J.Sutherland-Smith.

ABSTRACT

The filamin proteins cross-link F-actin and interact with protein partners to integrate both extracellular and intracellular signalling events with the cytoskeleton and to provide mechanoprotection and sensing to cells. The filamins are large, flexible, multi-domain homodimers with the interactions between domains important for protein function. The crystal structure of the N-terminal region of filamin B, containing the actin binding domain (ABD) and the first filamin repeat (FR1) domain, reveals an extended two-domain conformation with no interaction between the ABD and FR1 other than the connecting linker region. The two FLNB347 structures in the crystallographic asymmetric unit exhibit differing relative domain orientations providing the first high-resolution structural characterisation of a filamin inter-domain conformational change. The structure reveals a new hinge in the linker region between ABD and FR1 that is ideally positioned to orient the ABD for actin binding and adds to the previously described hinge regions, hinge 1 (between repeats 15 and 16) and hinge 2 (repeats 23 and 24), providing an additional mechanism by which filamin can exhibit inter-domain flexibility. The extended structure, with the absence of interactions between the domains, implies that any conformational rearrangements required for actin binding by the ABD, as observed for homologous proteins, can freely occur without being influenced by FR1. The ABD retains its previously observed compact conformation. FR1 exhibits a filamin immunoglobulin-like domain fold with a closed C-D β-strand groove, in contrast to filamin repeats that bind protein partners with this region of the domain surface.