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. Three major sites of interaction can be distinguished. These interactions include hydrogen bonds (twinfilin residues participating in interactions are colored in magenta) and hydrophobic contacts (actin residues participating in interactions are colored according to hydrophobic/polar)[5].
3D structures of twinfilin
Updated on 20-August-2024
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:https://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
