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Kotila T, Wioland H, Selvaraj M, Kogan K, Antenucci L, Jégou A, Huiskonen JT, Romet-Lemonne G, Lappalainen P
Nat Commun 13 (1) 3442 [2022-06-15; online 2022-06-15]
Actin polymerization generates forces for cellular processes throughout the eukaryotic kingdom, but our understanding of the 'ancient' actin turnover machineries is limited. We show that, despite > 1 billion years of evolution, pathogenic Leishmania major parasite and mammalian actins share the same overall fold and co-polymerize with each other. Interestingly, Leishmania harbors a simple actin-regulatory machinery that lacks cofilin 'cofactors', which accelerate filament disassembly in higher eukaryotes. By applying single-filament biochemistry we discovered that, compared to mammalian proteins, Leishmania actin filaments depolymerize more rapidly from both ends, and are severed > 100-fold more efficiently by cofilin. Our high-resolution cryo-EM structures of Leishmania ADP-, ADP-Pi- and cofilin-actin filaments identify specific features at actin subunit interfaces and cofilin-actin interactions that explain the unusually rapid dynamics of parasite actin filaments. Our findings reveal how divergent parasites achieve rapid actin dynamics using a remarkably simple set of actin-binding proteins, and elucidate evolution of the actin cytoskeleton.
PubMed 35705539
DOI 10.1038/s41467-022-31068-y
Crossref 10.1038/s41467-022-31068-y
pmc: PMC9200798
pii: 10.1038/s41467-022-31068-y