1.C.34 The Tachyplesin (Tachyplesin) Family

The tachyplesins are β-structured protegrin-like molecules that are produced in horseshoe crab hemocytes. They are found in hemocyte S-granules and are active against Gram-negative and Gram-positive bacteria, fungi and enveloped viruses such as HIV. They form transient anion-selective pores in phospholipid bilayers in a process that is facilitated by the application of a cis-negative membrane potential. They are cross linked by disulfide bridges. Tachyplesin I is a cyclic β-sheet antimicrobial.

It can both form pores and translocate across acidic phospholipid membranes. It shows high affinity for lipopolysaccharides (LPS) from Gram-negative bacteria (300x higher affinity than for acidic phospholipids). Linear tachyplesin analogues do not show this preferential affinity for LPS suggesting that the cyclic properties are important for macromolecular recognition and the biological activities (Hirakura et al., 2002).

The generalized reaction catalyzed by tachyplesins is: 

Small molecules (in) Small molecules (out)


 

References:

Edwards, I.A., A.G. Elliott, A.M. Kavanagh, M.A.T. Blaskovich, and M.A. Cooper. (2017). Structure-Activity and -Toxicity Relationships of the Antimicrobial Peptide Tachyplesin-1. ACS Infect Dis. [Epub: Ahead of Print]

Hirakura, Y., S. Kobayashi, and K. Matsuzaki (2002). Specific interactions of the antimicrobial peptide cyclic β- sheet tachyplesin I with lipopolysaccharides. Biochim Biophys Acta 1562: 32-6.

Lipkin, R., A. Pino-Angeles, and T. Lazaridis. (2017). Transmembrane Pore Structures of β-Hairpin Antimicrobial Peptides by All-Atom Simulations. J Phys Chem B 121: 9126-9140.

Matsuzaki, K. (1999). Why and how are peptide-lipid interactions utilized for self-defense? Magainins and tachyplesins as archetypes. Biochim Biophys. Acta 1462: 1-10.

Matsuzaki, K., S. Yoneyama, N. Fujii, K. Miyajima, K. Yamada, Y. Kirino, and K. Anzai. (1997). Membrane permeabilization mechanisms of a cyclic antimicrobial peptide, tachyplesin I, and its linear analog. Biochemistry 36: 9799-9806.

Tanner, J.D., E. Deplazes, and R.L. Mancera. (2018). The Biological and Biophysical Properties of the Spider Peptide Gomesin. Molecules 23:.

Zhang, S., L. Fu, M. Wan, J. Song, L. Gao, and W. Fang. (2019). Peripheral Antimicrobial Peptide Gomesin Induces Membrane Protrusion, Folding, and Laceration. Langmuir. [Epub: Ahead of Print]

Examples:

TC#NameOrganismal TypeExample
1.C.34.1.1

Tachyplesin I precursor.  It's 3-d pore structure has been examined (Lipkin et al. 2017). Its structure/function and toxicity activities have been reviewed (Edwards et al. 2017).

Horseshoe crabs

Tachyplesin I of Tachypleus tridentatus

 
Examples:

TC#NameOrganismal TypeExample
1.C.34.2.1Polyphemusin I Atlantic Horseshoe crabs Polyphemusin I of Limulus polyphemus
 
Examples:

TC#NameOrganismal TypeExample
1.C.34.3.1

Spider peptide, Gomesin, of 84 aas and 1 N-terminal TMS.  Gomesin is active against several Gram-positive bacteria such as Bacillus spp, Staphylococcus spp and E.faecalis, several Gram-negative bacteria such as E. coli, K. pneumoniae,   and Salmonella spp, filamentous fungi such as N. crassa, T. viridae and yeasts such as  C. albicans. It is active against the parasite L.amazonensis as well. Tanner et al. 2018 concluded that it is hemolytic, permeabilizing cell membranes, probably a pore former, but Zhang et al. 2019 concluded that it induces membrane protrusion, folding and laceration without forming pores.

Gomesin of Acanthoscurria gomesiana (Tarantula spider) (Phormictopus pheopygus)