PDBsum entry 1v05

Actin-binding protein

PDB id

1v05

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Contents

			Protein chain

					96 a.a. *

			Waters ×73

* Residue conservation analysis

PDB id:

1v05

Links

Name:

Actin-binding protein

Title:

Dimerization of human filamin c: crystal structure of the domain 24

Structure:

Filamin c. Chain: a. Fragment: rod domain, residues 2633-2725. Synonym: gamma-filamin, filamin 2, protein flnc, abp-l abp-280-like protein, actin-bindin like protein. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PDB file)

Resolution:

1.43Å

R-factor:

0.188

R-free:

0.205

Authors:

R.Pudas,T.-R.Kiema,J.Ylanne

Key ref:

R.Pudas et al. (2005). Structural basis for vertebrate filamin dimerization. Structure, 13, 111-119. PubMed id: 15642266 DOI: 10.1016/j.str.2004.10.014

Date:

22-Mar-04

Release date:

17-Nov-04

PROCHECK

	Headers

	References

Protein chain

Q14315 (FLNC_HUMAN) - Filamin-C from Homo sapiens

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:

Seq: Struc:					2725 a.a. 96 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1016/j.str.2004.10.014	Structure 13:111-119 (2005)
PubMed id: 15642266

Structural basis for vertebrate filamin dimerization.
R.Pudas, T.R.Kiema, P.J.Butler, M.Stewart, J.Ylänne.

ABSTRACT

Filamins are essential in cell motility and many developmental processes. They are large actin cross linking proteins that contain actin binding domains in their N termini and a long rod region constructed from 24 tandem Ig domains. Dimerization is crucial for the actin crosslinking function of filamins and requires the most C-terminal Ig domain. We describe here the crystal structure of this 24th Ig domain (Ig24) of human filamin C and show how it mediates dimerization. The dimer interface is novel and quite different to that seen in the Dictyostelium discoideum filamin analog. The sequence signature of the dimerization interface suggests that the C-terminal domains of all vertebrate filamins share the same dimerization mechanism. Furthermore, we show that point mutations in the dimerization interface disrupt the dimer and that the dissociation constant for recombinant Ig24 is in the micromolar range.

Selected figure(s)



	Figure 4. Figure 4. Filamin Domain 24 Dimerization Interface (A) The hydrophobic stacking of strand C in the dimer interface. Side chains of Met2669 pack against Gly2671 of the neighboring monomer, creating hydrophobic interactions. (B) Hydrogen bonding between the monomers at strand D.

Figure was selected by an automated process.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20061151

A.X.Zhou, J.H.Hartwig, and L.M.Akyürek (2010).
Filamins in cell signaling, transcription and organ development.

Trends Cell Biol, 20, 113-123.

19514078

B.A.Kesner, F.Ding, B.R.Temple, and N.V.Dokholyan (2010).
N-terminal strands of filamin Ig domains act as a conformational switch under biological forces.

Proteins, 78, 12-24.

20489725

F.Sauer, J.Vahokoski, Y.H.Song, and M.Wilmanns (2010).
Molecular basis of the head-to-tail assembly of giant muscle proteins obscurin-like 1 and titin.

EMBO Rep, 11, 534-540.

PDB code:

3knb

20713593

H.Falet, A.Y.Pollitt, A.J.Begonja, S.E.Weber, D.Duerschmied, D.D.Wagner, S.P.Watson, and J.H.Hartwig (2010).
A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function.

J Exp Med, 207, 1967-1979.

19293932

F.Nakamura, O.Heikkinen, O.T.Pentikäinen, T.M.Osborn, K.E.Kasza, D.A.Weitz, O.Kupiainen, P.Permi, I.Kilpeläinen, J.Ylänne, J.H.Hartwig, and T.P.Stossel (2009).
Molecular basis of filamin A-FilGAP interaction and its impairment in congenital disorders associated with filamin A mutations.

PLoS ONE, 4, e4928.

PDB code:

2k3t

20006946

H.S.Chen, K.S.Kolahi, and M.R.Mofrad (2009).
Phosphorylation facilitates the integrin binding of filamin under force.

Biophys J, 97, 3095-3104.

19137608

M.D.Seo, S.H.Seok, H.Im, A.R.Kwon, S.J.Lee, H.R.Kim, Y.Cho, D.Park, and B.J.Lee (2009).
Crystal structure of the dimerization domain of human filamin A.

Proteins, 75, 258-263.

PDB code:

3cnk

18996015

N.Pinotsis, P.Abrusci, K.Djinović-Carugo, and M.Wilmanns (2009).
Terminal assembly of sarcomeric filaments by intermolecular beta-sheet formation.

Trends Biochem Sci, 34, 33-39.

19828450

S.S.Ithychanda, D.Hsu, H.Li, L.Yan, D.D.Liu, D.Liu, M.Das, E.F.Plow, and J.Qin (2009).
Identification and characterization of multiple similar ligand-binding repeats in filamin: implication on filamin-mediated receptor clustering and cross-talk.

J Biol Chem, 284, 35113-35121.

19074766

S.S.Ithychanda, M.Das, Y.Q.Ma, K.Ding, X.Wang, S.Gupta, C.Wu, E.F.Plow, and J.Qin (2009).
Migfilin, a molecular switch in regulation of integrin activation.

J Biol Chem, 284, 4713-4722.

PDB code:

2k9u

17635842

C.Farrington-Rock, V.Kirilova, L.Dillard-Telm, A.D.Borowsky, S.Chalk, M.J.Rock, D.H.Cohn, and D.Krakow (2008).
Disruption of the Flnb gene in mice phenocopies the human disease spondylocarpotarsal synostosis syndrome.

Hum Mol Genet, 17, 631-641.

18059477

N.Pinotsis, S.Lange, J.C.Perriard, D.I.Svergun, and M.Wilmanns (2008).
Molecular basis of the C-terminal tail-to-tail assembly of the sarcomeric filament protein myomesin.

EMBO J, 27, 253-264.

PDB code:

2r15

18829455

Y.Lad, P.Jiang, S.Ruskamo, D.S.Harburger, J.Ylänne, I.D.Campbell, and D.A.Calderwood (2008).
Structural Basis of the Migfilin-Filamin Interaction and Competition with Integrin {beta} Tails.

J Biol Chem, 283, 35154-35163.

PDB code:

2w0p

17401197

A.H.Aguda, A.M.Sakwe, L.Rask, and R.C.Robinson (2007).
Expression, crystallization and preliminary crystallographic data analysis of filamin A repeats 14-16.

Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 291-293.

18056414

F.Nakamura, T.M.Osborn, C.A.Hartemink, J.H.Hartwig, and T.P.Stossel (2007).
Structural basis of filamin A functions.

J Cell Biol, 179, 1011-1025.

17690686

Y.Lad, T.Kiema, P.Jiang, O.T.Pentikäinen, C.H.Coles, I.D.Campbell, D.A.Calderwood, and J.Ylänne (2007).
Structure of three tandem filamin domains reveals auto-inhibition of ligand binding.

EMBO J, 26, 3993-4004.

PDB code:

2j3s

16752402

C.Farrington-Rock, M.H.Firestein, L.S.Bicknell, A.Superti-Furga, C.A.Bacino, V.Cormier-Daire, M.Le Merrer, C.Baumann, J.Roume, P.Rump, J.B.Verheij, E.Sweeney, D.L.Rimoin, R.S.Lachman, S.P.Robertson, D.H.Cohn, and D.Krakow (2006).
Mutations in two regions of FLNB result in atelosteogenesis I and III.

Hum Mutat, 27, 705-710.

16293600

F.Nakamura, R.Pudas, O.Heikkinen, P.Permi, I.Kilpeläinen, A.D.Munday, J.H.Hartwig, T.P.Stossel, and J.Ylänne (2006).
The structure of the GPIb-filamin A complex.

Blood, 107, 1925-1932.

PDB codes:

2aav 2bp3

16781869

G.M.Popowicz, M.Schleicher, A.A.Noegel, and T.A.Holak (2006).
Filamins: promiscuous organizers of the cytoskeleton.

Trends Biochem Sci, 31, 411-419.

16455489

T.Kiema, Y.Lad, P.Jiang, C.L.Oxley, M.Baldassarre, K.L.Wegener, I.D.Campbell, J.Ylänne, and D.A.Calderwood (2006).
The molecular basis of filamin binding to integrins and competition with talin.

Mol Cell, 21, 337-347.

PDB code:

2brq

15929027

M.Vorgerd, P.F.van der Ven, V.Bruchertseifer, T.Lowe, R.A.Kley, R.Schroder, H.Lochmuller, M.Himmel, K.Koehler, D.O.Furst, and A.Huebner (2005).
A mutation in the dimerization domain of filamin c causes a novel type of autosomal dominant myofibrillar myopathy.

Am J Hum Genet, 77, 297-304.

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.