6QRI

Structure of rabbit G-actin in complex with chivosazole A

Summary for 6QRI

• Entry DOI: 10.2210/pdb6qri/pdb
• Descriptor: Actin, alpha skeletal muscle, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: cytoskeleton, macrolide, myxobacteria, cytosolic protein
• Biological source: Oryctolagus cuniculus (Rabbit)
• Total number of polymer chains: 2
• Total formula weight: 87015.09

Authors

Schneider, S.,Wang, S.,Zahler, S. (deposition date: 2019-02-19, release date: 2019-07-03, Last modification date: 2024-01-24)

Primary citation

Wang, S.,Gegenfurtner, F.A.,Crevenna, A.H.,Ziegenhain, C.,Kliesmete, Z.,Enard, W.,Muller, R.,Vollmar, A.M.,Schneider, S.,Zahler, S.
Chivosazole A Modulates Protein-Protein Interactions of Actin.
J.Nat.Prod., 82:1961-1970, 2019

PubMed Abstract: Actin is a protein of central importance for many cellular key processes. It is regulated by local interactions with a large number of actin binding proteins (ABPs). Various compounds are known to either increase or decrease the polymerization dynamics of actin. However, no actin binding compound has been developed for clinical applications yet because of selectivity issues. We provide a crystal structure of the natural product chivosazole A (ChivoA) bound to actin and show that-in addition to inhibiting nucleation, polymerization, and severing of F-actin filaments-it selectively modulates binding of ABPs to G-actin: Although unphysiological actin dimers are induced by ChivoA, interaction with gelsolin, profilin, cofilin, and thymosin-β4 is inhibited. Moreover, ChivoA causes transcriptional effects differing from latrunculin B, an actin binder with a different binding site. Our data show that ChivoA and related compounds could serve as scaffolds for the development of actin binding molecules selectively targeting specific actin functions.

PubMed: 31260301
DOI: 10.1021/acs.jnatprod.9b00335

Experimental method

X-RAY DIFFRACTION (2.4 Å)