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The Functionality of Membrane-Inserting Proteins and Peptides: Curvature Sensing, Generation, and Pore Formation

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Abstract

Proteins and peptides with hydrophobic and amphiphilic segments are responsible for many biological functions. The sensing and generation of membrane curvature are the functions of several protein domains or motifs. While some specific membrane proteins play an essential role in controlling the curvature of distinct intracellular membranes, others participate in various cellular processes such as clathrin-mediated endocytosis, where several proteins sort themselves at the neck of the membrane bud. A few membrane-inserting proteins form nanopores that permeate selective ions and water to cross the membrane. In addition, many natural and synthetic small peptides and protein toxins disrupt the membrane by inducing nonspecific pores in the membrane. The pore formation causes cell death through the uncontrolled exchange between interior and exterior cellular contents. In this article, we discuss the insertion depth and orientation of protein/peptide helices, and their role as a sensor and inducer of membrane curvature as well as a pore former in the membrane. We anticipate that this extensive review will assist biophysicists to gain insight into curvature sensing, generation, and pore formation by membrane insertion.

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Acknowledgements

We gladly acknowledge IIT Palakkad’s faculty seed grant and the Ministry of Human Resource Development’s (MHRD) grant Scheme for Transformational and Advanced Research in Sciences (STARS) for financial support. CH is grateful for the interesting conversation with Dr. Bibhuti Ranjan Mishra at IIT Palakkad, particularly about the pore formation mechanism. The reviewers’ thorough reading and insightful comments, which greatly enhanced this manuscript’s readability, are greatly appreciated by the authors.

Funding

Funding was received from the MHRD grant Scheme for Transformational and Advanced Research in Sciences (Grant No. STARS/APR2019/293).

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CH prepared all the figures and wrote the whole manuscript. SLD thoroughly reviewed the manuscript and suggested major modifications/corrections.

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Correspondence to Chandra Has.

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The authors do not have any conflict of interest.

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Has, C., Das, S.L. The Functionality of Membrane-Inserting Proteins and Peptides: Curvature Sensing, Generation, and Pore Formation. J Membrane Biol 256, 343–372 (2023). https://doi.org/10.1007/s00232-023-00289-7

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  • DOI: https://doi.org/10.1007/s00232-023-00289-7

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