Structural journey of an insecticidal protein against western corn rootworm

Marini, G. and Poland, B. and Leininger, C. and Lukoyanova, N. and Spielbauer, D. and Barry, J.K. and Altier, D. and Lum, A. and Scolaro, E. and Ortega, C.P. and Yalpani, N. and Sandahl, G. and Mabry, T. and Klever, J. and Nowatzki, T. and Zhao, J.-Z. and Sethi, A. and Kassa, A. and Crane, V. and Lu, A.L. and Nelson, M.E. and Eswar, N. and Topf, Maya and Saibil, Helen (2023) Structural journey of an insecticidal protein against western corn rootworm. Nature Communications 14 (1), ISSN 2041-1723.

Abstract

The broad 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 those utilized for existing transgenic traits. We identified an insecticidal membrane attack complex/perforin (MACPF) protein, Mpf2Ba1, with strong activity against the devastating coleopteran pest western corn rootworm (WCR) and a novel site of action. Using an integrative structural biology approach, we determined monomeric, pre-pore and pore structures, revealing changes between structural states at high resolution. We discovered an assembly inhibition mechanism, a molecular switch that activates pre-pore oligomerization upon gut fluid incubation and solved the highest resolution MACPF pore structure to-date. Our findings demonstrate not only the utility of Mpf2Ba1 in the development of biotechnology solutions for protecting maize from WCR to promote food security, but also uncover previously unknown mechanistic principles of bacterial MACPF assembly.

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