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Sequence Diversity in the Pore-Forming Motifs of the Membrane-Damaging Protein Toxins

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Abstract

Pore-forming proteins/toxins (PFPs/PFTs) are the distinct class of membrane-damaging proteins. They act by forming oligomeric pores in the plasma membranes. PFTs and PFPs from diverse organisms share a common mechanism of action, in which the designated pore-forming motifs of the membrane-bound protein molecules insert into the membrane lipid bilayer to create the water-filled pores. One common characteristic of these pore-forming motifs is that they are amphipathic in nature. In general, the hydrophobic sidechains of the pore-forming motifs face toward the hydrophobic core of the membranes, while the hydrophilic residues create the lining of the water-filled pore lumen. Interestingly, pore-forming motifs of the distinct subclass of PFPs/PFTs share very little sequence similarity with each other. Therefore, the common guiding principle that governs the sequence-to-structure paradigm in the mechanism of action of these PFPs/PFTs still remains an enigma. In this article, we discuss this notion using the examples of diverse groups of membrane-damaging PFPs/PFTs.

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Funding

We acknowledge funding under the Centre of Excellence (COE) in the Frontier Areas of Science and Technology (FAST) program of the Ministry of Human Resource Development, Govt. of India, in the area of protein science, design, and engineering. We also thank Indian Institute of Science Education and Research Mohali for support; Research fellowships from the Council of Scientific and Industrial Research (CSIR), India (to A.K.M. and K.L.), University Grants Commission, India (to P.V. and S.C.), and Department of Biotechnology, India (to M.S.) are also acknowledged.

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  1. Centre for Protein Science, Design and Engineering, Department of Biological Sciences, Indian Institute of Science Education and Research Mohali, Sector 81, S. A. S. Nagar, Manauli, Mohali, Punjab, 140306, India

    Anish Kumar Mondal, Pratima Verma, Kusum Lata, Mahendra Singh, Shamaita Chatterjee & Kausik Chattopadhyay

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  1. Anish Kumar Mondal
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  2. Pratima Verma
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Correspondence to Kausik Chattopadhyay.

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Mondal, A.K., Verma, P., Lata, K. et al. Sequence Diversity in the Pore-Forming Motifs of the Membrane-Damaging Protein Toxins. J Membrane Biol 253, 469–478 (2020). https://doi.org/10.1007/s00232-020-00141-2

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