Function
Twinfilin (Twi) is an actin-monomer-binding protein which is composed of 2 Actin Depolimerizing Factor Homology (ADF-H) domains. Twi forms a 1:1 complex with ADP-actin-monomer, inhibits nucleotide exchange on actin monomers and prevents assembly of the monomer to filaments[1].
- Twinfilin 1 is an actin-depolymerisation factor regulating actin filament assembly [2].
- Twinfilin 2 regulates stereocilia elongation for maintaining the architecture of cochlear hair bundles[3].
Relevance
Twi-1 is highly induced by stimulation of amino acids (Met and Leu) and hormones(estrogen and prolactin) and involved in regulation of milk biosynthesis[4].
Structural highlights
The twinfilin-1 C-terminal ADF-H domain binds to a groove between two subdomains of actin. . These interactions include (twinfilin residues participating in interactions are colored in magenta) and (actin residues participating in interactions are colored according to hydrophobic/polar)[5].
3D structures of twinfilin
Updated on 04-May-2025
Domains: N-terminal ADF-H 1-142; C-terminal ADF-H 176-316
2vac – hTwi-2 N-terminal ADF-H domain - human
2w0i – hTwi-2 C-terminal ADF-H domain (mutant)
7ccc – hTwi-1 + F-actin-capping protein + actin
2hd7, 2d8b – mTwi-1 C-terminal ADF-H domain – mouse - NMR
1m4j – mTwi-1 N-terminal ADF-H domain
6rsw – mTwi-1 C-terminal ADF-H domain + actin + CAP1
7ds2 – mTwi-1 C-terminal + F-actin-capping protein
7ds4 – mTwi-1 C-terminal (mutant) + F-actin-capping protein
7dsb – mTwi-1 C-terminal + F-actin-capping protein + myotrophin
7ds3 – mTwi-2 + F-actin-capping protein
6yp9 – rTwi-1 C-terminal ADF-H domain + actin - rabbit
3daw – rTwi-1 C-terminal ADF-H domain (mutant) + actin + ATP
6k2f – Twi – Entamoeba histolytica
References
- ↑ Palmgren S, Vartiainen M, Lappalainen P. Twinfilin, a molecular mailman for actin monomers. J Cell Sci. 2002 Mar 1;115(Pt 5):881-6. PMID:11870207
- ↑ Nguyen MT, Won YH, Kwon TW, Lee W. Twinfilin-1 is an essential regulator of myogenic differentiation through the modulation of YAP in C2C12 myoblasts. Biochem Biophys Res Commun. 2022 Apr 9;599:17-23. PMID:35168059 doi:10.1016/j.bbrc.2022.02.021
- ↑ Peng AW, Belyantseva IA, Hsu PD, Friedman TB, Heller S. Twinfilin 2 regulates actin filament lengths in cochlear stereocilia. J Neurosci. 2009 Dec 2;29(48):15083-8. PMID:19955359 doi:10.1523/JNEUROSCI.2782-09.2009
- ↑ Li L, Liu L, Qu B, Li X, Gao X, Zhang M. Twinfilin 1 enhances milk bio-synthesis and proliferation of bovine mammary epithelial cells via the mTOR signaling pathway. Biochem Biophys Res Commun. 2017 Oct 21;492(3):289-294. doi:, 10.1016/j.bbrc.2017.08.130. Epub 2017 Aug 31. PMID:28864421 doi:http://dx.doi.org/10.1016/j.bbrc.2017.08.130
- ↑ Paavilainen VO, Oksanen E, Goldman A, Lappalainen P. Structure of the actin-depolymerizing factor homology domain in complex with actin. J Cell Biol. 2008 Jul 14;182(1):51-9. PMID:18625842 doi:10.1083/jcb.200803100