Mahendran, K R. (2020) Design and Assembly of Transmembrane Helix Barrel. The Journal of Membrane Biology. pp. 491-497. ISSN 1432-1424

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Abstract

Membrane-spanning proteins account for one-third of all proteins across all genomes involved in regulating the transport of a wide variety of molecules such as nutrients, ions, drugs and biomolecules into the cells (Nikaido 2003, Bayley and Jayasinghe 2004, Pages et al. 2008, Dal Peraro and van der Goot 2016). The majority of natural membrane proteins are α-helical and usually hydrophobic or amphipathic (von Heijne 2006; Bayley 2009). Redesigning membrane proteins is one of the main approaches within the engineering field to modify proteins into useful biomaterials for applications in biotechnology (Bayley and Jayasinghe 2004; Majd et al. 2010; Aksoyoglu et al. 2016; Ayub and Bayley 2016; Kasianowicz et al. 2016; Wang et al. 2018). Previously engineering efforts in this area have focused mainly on β-barrel membrane protein pores such as α-hemolysin (αHL), as they can be engineered with atomic precision for the single-molecule detection of a diverse range of analytes (Kasianowicz et al. 1996, 2016; Song et al. 1996; Bayley and Cremer 2001; Venkatesan and Bashir 2011; Bayley 2015; Ayub and Bayley 2016; Qing et al. 2018). However, the use of narrow non-selective pores has limited the nanopore technology and therefore engineering pores with novel structural conformation would expand the scope of single-molecule chemical and biosensing (Ayub and Bayley 2016; Howorka 2017). While β-barrels have been engineered extensively, membrane pores based on α-helices remain relatively unexplored (Zaccai et al. 2011; Woolfson et al. 2015; Woolfson 2017). Most of the natural ion channels consist of α-helical bundles and charge selectivity as observed in ion channels has not been produced with β-barrel pores (Benz et al. 1985; Doyle et al. 1998; Gu et al. 2000; Tajkhorshid et al. 2002; Derrington et al. 2010; Behrends 2012). Notably, α-helical pore-forming proteins include a broad range of antimicrobial peptides (AMPs) and pore-forming toxins (PFTs) and it has been difficult to define the pore structures due to the dynamic membrane assembly mechanism (Brogden 2005, Song et al. 2013, Leung et al. 2014, Dal Peraro and van der Goot 2016, Leung et al. 2017). Notably, redesigning α-helical bundles from existing scaffolds can cause misfolding leading to non-functional proteins and, therefore, they are mainly engineered by de novo design (Lear et al. 1988; Bayley and Jayasinghe 2004; Zaccai et al. 2011). The de novo design of water-soluble proteins has progressed rapidly, but membrane protein design is less developed and challenging (Joh et al. 2014; Thomson et al. 2014; Lu et al. 2018). Nevertheless, there has been significant interest in building α-helix-based transmembrane assemblies that selectively conduct small molecules (Soskine et al. 2013; Ayub and Bayley 2016; Howorka 2017; Mahendran et al. 2017; Krishnan et al. 2019). Moreover, the assembly of designed α-helical peptides may contribute to our understanding of the mechanism of action of amphipathic antimicrobial peptides (Puthumadathil et al. 2019).

Item Type:	Article
Subjects:	Genomics Facility
Depositing User:	Central Library RGCB
Date Deposited:	22 Jan 2021 06:45
Last Modified:	22 Jan 2021 06:46
URI:	http://rgcb.sciencecentral.in/id/eprint/1014

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