8C47
Leishmania ATP-actin monomer in complex with Leishmania profilin
Summary for 8C47
| Entry DOI | 10.2210/pdb8c47/pdb |
| Descriptor | Profilin, Actin, GLYCEROL, ... (6 entities in total) |
| Functional Keywords | actin, profilin, leishmania, cytoskeleton, structural protein |
| Biological source | Leishmania major More |
| Total number of polymer chains | 2 |
| Total formula weight | 58849.15 |
| Authors | |
| Primary citation | Vizcaino-Castillo, A.,Kotila, T.,Kogan, K.,Yanase, R.,Como, J.,Antenucci, L.,Michelot, A.,Sunter, J.D.,Lappalainen, P. Leishmania profilin interacts with actin through an unusual structural mechanism to control cytoskeletal dynamics in parasites. J.Biol.Chem., 300:105740-105740, 2024 Cited by PubMed Abstract: Diseases caused by Leishmania and Trypanosoma parasites are a major health problem in tropical countries. Because of their complex life cycle involving both vertebrate and insect hosts, and >1 billion years of evolutionarily distance, the cell biology of trypanosomatid parasites exhibits pronounced differences to animal cells. For example, the actin cytoskeleton of trypanosomatids is divergent when compared with other eukaryotes. To understand how actin dynamics are regulated in trypanosomatid parasites, we focused on a central actin-binding protein profilin. Co-crystal structure of Leishmania major actin in complex with L. major profilin revealed that, although the overall folds of actin and profilin are conserved in eukaryotes, Leishmania profilin contains a unique α-helical insertion, which interacts with the target binding cleft of actin monomer. This insertion is conserved across the Trypanosomatidae family and is similar to the structure of WASP homology-2 (WH2) domain, a small actin-binding motif found in many other cytoskeletal regulators. The WH2-like motif contributes to actin monomer binding and enhances the actin nucleotide exchange activity of Leishmania profilin. Moreover, Leishmania profilin inhibited formin-catalyzed actin filament assembly in a mechanism that is dependent on the presence of the WH2-like motif. By generating profilin knockout and knockin Leishmania mexicana strains, we show that profilin is important for efficient endocytic sorting in parasites, and that the ability to bind actin monomers and proline-rich proteins, and the presence of a functional WH2-like motif, are important for the in vivo function of Leishmania profilin. Collectively, this study uncovers molecular principles by which profilin regulates actin dynamics in trypanosomatids. PubMed: 38340794DOI: 10.1016/j.jbc.2024.105740 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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