| Structural highlights
Function
MTPN_HUMAN Promotes dimerization of NF-kappa-B subunits and regulates NF-kappa-B transcription factor activity (By similarity). Plays a role in the regulation of the growth of actin filaments. Inhibits the activity of the F-actin-capping protein complex formed by the CAPZA1 and CAPZB heterodimer. Promotes growth of cardiomyocytes, but not cardiomyocyte proliferation. Promotes cardiac muscle hypertrophy.[1] [2] [3]
Publication Abstract from PubMed
V-1, also known as myotrophin, is a 13 kDa ankyrin-repeat protein that binds and inhibits the heterodimeric actin capping protein (CP), which is a key regulator of cytoskeletal actin dynamics. The crystal structure of V-1 in complex with CP revealed that V-1 recognizes CP via residues spanning several ankyrin repeats. Here, the crystal structure of human V-1 is reported in the absence of the specific ligand at 2.3 A resolution. In the asymmetric unit, the crystal contains two V-1 monomers that exhibit nearly identical structures (C(alpha) r.m.s.d. of 0.47 A). The overall structures of the two apo V-1 chains are also highly similar to that of CP-bound V-1 (C(alpha) r.m.s.d.s of <0.50 A), indicating that CP does not induce a large conformational change in V-1. Detailed structural comparisons using the computational program All Atom Motion Tree revealed that CP binding can be accomplished by minor side-chain rearrangements of several residues. These findings are consistent with the known biological role of V-1, in which it globally inhibits CP in the cytoplasm.
Crystal structure of human V-1 in the apo form.,Takeda S, Koike R, Nagae T, Fujiwara I, Narita A, Maeda Y, Ota M Acta Crystallogr F Struct Biol Commun. 2021 Jan 1;77(Pt 1):13-21. doi:, 10.1107/S2053230X20016829. Epub 2021 Jan 1. PMID:33439151[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Anderson KM, Berrebi-Bertrand I, Kirkpatrick RB, McQueney MS, Underwood DC, Rouanet S, Chabot-Fletcher M. cDNA sequence and characterization of the gene that encodes human myotrophin/V-1 protein, a mediator of cardiac hypertrophy. J Mol Cell Cardiol. 1999 Apr;31(4):705-19. PMID:10329199 doi:http://dx.doi.org/10.1006/jmcc.1998.0903
- ↑ Bhattacharya N, Ghosh S, Sept D, Cooper JA. Binding of myotrophin/V-1 to actin-capping protein: implications for how capping protein binds to the filament barbed end. J Biol Chem. 2006 Oct 13;281(41):31021-30. Epub 2006 Aug 7. PMID:16895918 doi:http://dx.doi.org/10.1074/jbc.M606278200
- ↑ Takeda S, Minakata S, Koike R, Kawahata I, Narita A, Kitazawa M, Ota M, Yamakuni T, Maeda Y, Nitanai Y. Two distinct mechanisms for actin capping protein regulation--steric and allosteric inhibition. PLoS Biol. 2010 Jul 6;8(7):e1000416. PMID:20625546 doi:10.1371/journal.pbio.1000416
- ↑ Takeda S, Koike R, Nagae T, Fujiwara I, Narita A, Maéda Y, Ota M. Crystal structure of human V-1 in the apo form. Acta Crystallogr F Struct Biol Commun. 2021 Jan 1;77(Pt 1):13-21. PMID:33439151 doi:10.1107/S2053230X20016829
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