3M6G

Crystal structure of actin in complex with lobophorolide

Summary for 3M6G

• Entry DOI: 10.2210/pdb3m6g/pdb
• Related: 1QZ5 1YXQ 2ASM 2ASO 2ASP 2VYP
• Descriptor: Actin, alpha skeletal muscle, MAGNESIUM ION, ADENOSINE-5'-TRIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: actin, macrolide, lobophorolide, actin dimer, marine toxin, atp-binding, cytoskeleton, muscle protein, nucleotide-binding, structural protein
• Biological source: Oryctolagus cuniculus (rabbit)
• Cellular location: Cytoplasm, cytoskeleton: P68135
• Total number of polymer chains: 2
• Total formula weight: 85409.12

Authors

Allingham, J.S. (deposition date: 2010-03-15, release date: 2010-09-08, Last modification date: 2024-03-13)

Primary citation

Blain, J.C.,Mok, Y.F.,Kubanek, J.,Allingham, J.S.
Two molecules of lobophorolide cooperate to stabilize an actin dimer using both their "ring" and "tail" region.
Chem.Biol., 17:802-807, 2010

PubMed Abstract: Actin filament-disrupting marine macrolides are promising templates from which to design therapeutics against cancer and other diseases that co-opt the actin cytoskeleton. Typically, these macrolides form either a 1:1 or 2:1 actin-macrolide complex where their aliphatic side chain, or "tail," has been reported to convey the major determinant of cytotoxicity. We now report the structure of the marine macrolide lobophorolide bound to actin with a unique 2:2 stoichiometry in which two lobophorolide molecules cooperate to form a dimerization interface that is composed entirely of the macrolide "ring" region, and each molecule of lobophorolide interacts with both actin subunits via their ring and tail regions to tether the subunits together. This binding mode imposes multiple barriers against microfilament stability and holds important implications for development of actin-targeting drugs and the evolution of macrolide biosynthetic enzymes.

PubMed: 20797609
DOI: 10.1016/j.chembiol.2010.06.010

Experimental method

X-RAY DIFFRACTION (2 Å)