6iqf
crystal structure of Arabidopsis thaliana Profilin 3
Structural highlights
FunctionPRF3_ARATH Binds to actin monomers and regulates the organization of the actin cytoskeleton (PubMed:23052593, PubMed:29861135). Can increase the critical concentration (Cc) of actin assembly in vitro (PubMed:23052593). Acts as downstream effector of the hydrogen sulfide signaling to regulate the assembly and depolymerization of F-actin (PubMed:25652660). At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations (Probable). Binding to the poly-proline motif of formin induces oligomerization of PRF3 (PubMed:29861135). PRF3 oligomers inhibit formin-mediated actin assembly to modulate plant immunity triggered by pathogen-associated molecular patterns (PAMPs) (PubMed:29861135).[1] [2] [3] [4] Publication Abstract from PubMedProfilins are abundant cytosolic proteins that are universally expressed in eukaryotes and regulate actin filament elongation by binding to both monomeric actin (G-actin) and formin proteins. The atypical profilin Arabidopsis AtPRF3 has been reported to cooperate with canonical profilin isoforms in suppressing formin-mediated actin polymerization during plant innate immunity responses. AtPRF3 has a 37-amino-acid-long N terminal extension (NTE), and its suppressive effect on actin assembly is derived from enhanced interaction with the poly-proline (Poly-P) of the formin AtFH1. However, the molecular mechanism remains unclear. Here, we solved the crystal structures of AtPRF3Delta22 and AtPRF3Delta37, as well as AtPRF2 apo form and in complex with AtFH1 Poly-P at 1.5-3.6 A resolutions. By combining these structures with molecular modeling, we found that AtPRF3Delta22 NTE has high plasticity, with a primary "closed" conformation that can adopt an open conformation that enables Poly-P binding. Furthermore, using molecular dynamics simulation and free-energy calculations of protein-protein binding, along with experimental validation, we show that the AtPRF3Delta22 binds to Poly-P in an adaptive manner, thereby enabling different binding modes that maintain the interaction through disordered sequences. Together, our structural and simulation results suggest that the dynamic conformational changes of the AtPRF3 NTE upon Poly-P binding modulate their interactions to fine-tune formin-mediated actin assembly. Structural and computational examination of the Arabidopsis profilin-Poly-P complex reveals mechanistic details in profilin-regulated actin assembly.,Qiao Z, Sun H, Ng JTY, Ma Q, Koh SH, Mu Y, Miao Y, Gao YG J Biol Chem. 2019 Oct 25. pii: RA119.011307. doi: 10.1074/jbc.RA119.011307. PMID:31653702[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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