7M0G

Magic Angle Spinning NMR Structure of Human Cofilin-2 Assembled on Actin Filaments

Summary for 7M0G

• Entry DOI: 10.2210/pdb7m0g/pdb
• NMR Information: BMRB: 30877
• Descriptor: Cofilin-2 (1 entity in total)
• Functional Keywords: actin filament binding, actin filament severing, cytoskeletal assembly, contractile protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 18765.63

Authors

Kraus, J.,Polenova, T.,Perilla, J.P.,Xu, C. (deposition date: 2021-03-10, release date: 2022-04-20, Last modification date: 2024-05-15)

Primary citation

Kraus, J.,Russell, R.W.,Kudryashova, E.,Xu, C.,Katyal, N.,Perilla, J.R.,Kudryashov, D.S.,Polenova, T.
Magic angle spinning NMR structure of human cofilin-2 assembled on actin filaments reveals isoform-specific conformation and binding mode.
Nat Commun, 13:2114-2114, 2022

PubMed Abstract: Actin polymerization dynamics regulated by actin-binding proteins are essential for various cellular functions. The cofilin family of proteins are potent regulators of actin severing and filament disassembly. The structural basis for cofilin-isoform-specific severing activity is poorly understood as their high-resolution structures in complex with filamentous actin (F-actin) are lacking. Here, we present the atomic-resolution structure of the muscle-tissue-specific isoform, cofilin-2 (CFL2), assembled on ADP-F-actin, determined by magic-angle-spinning (MAS) NMR spectroscopy and data-guided molecular dynamics (MD) simulations. We observe an isoform-specific conformation for CFL2. This conformation is the result of a unique network of hydrogen bonding interactions within the α2 helix containing the non-conserved residue, Q26. Our results indicate F-site interactions that are specific between CFL2 and ADP-F-actin, revealing mechanistic insights into isoform-dependent F-actin disassembly.

PubMed: 35440100
DOI: 10.1038/s41467-022-29595-9

Experimental method

SOLID-STATE NMR