Structural journey of an insecticidal pore-forming protein targeting western corn rootworm

Author:

Marini G.,Poland B.,Leininger C.,Lukoyanova N.,Spielbauer D.,Barry J.,Altier D.,Lum A.,Scolaro E.,Pérez Ortega C.,Yalpani N.,Sandahl G.,Mabry T.,Klever J.,Nowatzki T.,Zhao J-Z.,Sethi A.,Kassa A.,Crane V.,Lu A.,Nelson M.E.,Eswar N.,Topf M.,Saibil H.R.ORCID

Abstract

AbstractBroad adoption of transgenic crops has revolutionized agriculture. However, resistance to insecticidal proteins by agricultural pests poses a continuous challenge to maintaining crop productivity and new proteins are urgently needed to replace existing transgenic traits. We identified an insecticidal membrane attack complex/perforin (MACPF) protein, Mpf2Ba1, with strong activity against western corn rootworm larvae and a novel site of action. By integrating X-ray crystallography, cryo-EM, and modelling, we determined monomeric, pre-pore and pore structures, revealing changes between structural states at atomic resolution. We discovered a monomer inhibition mechanism, a molecular “switch” associated with pre-pore activation/oligomerization upon gut fluid incubation and solved the highest resolution MACPF pore structure to-date. Our findings provide a mechanistic basis for Mpf2Ba1 effectiveness as an insecticidal protein with potential for biotechnology development.One-Sentence SummaryThe molecular mechanism of an insecticidal protein is revealed through 3D structures of the three main pore formation states

Publisher

Cold Spring Harbor Laboratory

Reference83 articles.

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