Structures of calmodulin–melittin complexes show multiple binding modes lacking classical anchoring interactions

Dürvanger, Zsolt; Juhász, Tünde; Liliom, Károly; Harmat, Veronika

doi:10.1016/j.jbc.2023.104596

Cited by 5 publications

(3 citation statements)

References 87 publications

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“…4c illustrates the ellipsoid shape of 4Ca 2+ –CaM–Mel, which was also compared with its crystal structure in the PDB (). 79 Instead of “jumping” between two conformations, CaM–Mel complexes adopt a relatively stable, closed conformation.…”

Section: Resultsmentioning

confidence: 99%

Mobility capillary electrophoresis–native mass spectrometry reveals the dynamic conformational equilibrium of calmodulin and its complexes

Zhao,

Zhang,

Hong

et al. 2024

Analyst

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Section: Resultsmentioning

confidence: 99%

Mobility capillary electrophoresis–native mass spectrometry reveals the dynamic conformational equilibrium of calmodulin and its complexes

Zhao,

Zhang,

Hong

et al. 2024

Analyst

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“…Whereas the helical structure of MEL remains, the swapping of its salt bridges and partial unfolding of its C-terminal segment can occur. Different sets of residues can anchor at the hydrophobic pockets of calmodulin, which are considered the main recognition sites [ 160 ]. A block of calmodulin can cause disruptions of the PI3K/Akt and other pathways caused by BV; numerous data have been summarized in recent exhaustive reports [ 22 , 145 ].…”

Section: Anticancer Effects Of Bee Venom and Its Componentsmentioning

confidence: 99%

Bee Venom: Composition and Anticancer Properties

Gajski,

Leonova,

Sjakste

2024

Toxins

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Among the various natural compounds used in alternative and Oriental medicine, toxins isolated from different organisms have had their application for many years, and Apis mellifera venom has been studied the most extensively. Numerous studies dealing with the positive assets of bee venom (BV) indicated its beneficial properties. The usage of bee products to prevent the occurrence of diseases and for their treatment is often referred to as apitherapy and is based mainly on the experience of the traditional system of medical practice in diverse ethnic communities. Today, a large number of studies are focused on the antitumor effects of BV, which are mainly attributed to its basic polypeptide melittin (MEL). Previous studies have indicated that BV and its major constituent MEL cause a strong toxic effect on different cancer cells, such as liver, lung, bladder, kidney, prostate, breast, and leukemia cells, while a less pronounced effect was observed in normal non-target cells. Their proposed mechanisms of action, such as the effect on proliferation and growth inhibition, cell cycle alterations, and induction of cell death through several cancer cell death mechanisms, are associated with the activation of phospholipase A2 (PLA2), caspases, and matrix metalloproteinases that destroy cancer cells. Numerous cellular effects of BV and MEL need to be elucidated on the molecular level, while the key issue has to do with the trigger of the apoptotic cascade. Apoptosis could be either a consequence of the plasmatic membrane fenestration or the result of the direct interaction of the BV components with pro-apoptotic and anti-apoptotic factors. The interaction of BV peptides and enzymes with the plasma membrane is a crucial step in the whole process. However, before its possible application as a remedy, it is crucial to identify the correct route of exposure and dosage of BV and MEL for potential therapeutic use as well as potential side effects on normal cells and tissues to avoid any possible adverse event.

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“…Melittin is also applied for the studies related to calmodulin (CaM), a sensor protein of calcium ions, which is regarded as hub protein to bind and modulate more than 200 target proteins in a concentration-dependent manner of calcium ions. Recently, it is reported that the interaction of melittin and CaM is through melittin anchoring at the hydrophobic pockets of CaM by different sets of residues responding to different conformers ( 16 ). The multiple binding modes of melittin-CaM suggest the multiple target potential.…”

Section: Introductionmentioning

confidence: 99%

The current landscape of the antimicrobial peptide melittin and its therapeutic potential

Zhang,

Sun,

et al. 2024

Front. Immunol.

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Melittin, a main component of bee venom, is a cationic amphiphilic peptide with a linear α-helix structure. It has been reported that melittin can exert pharmacological effects, such as antitumor, antiviral and anti-inflammatory effects in vitro and in vivo. In particular, melittin may be beneficial for the treatment of diseases for which no specific clinical therapeutic agents exist. Melittin can effectively enhance the therapeutic properties of some first-line drugs. Elucidating the mechanism underlying melittin-mediated biological function can provide valuable insights for the application of melittin in disease intervention. However, in melittin, the positively charged amino acids enables it to directly punching holes in cell membranes. The hemolysis in red cells and the cytotoxicity triggered by melittin limit its applications. Melittin-based nanomodification, immuno-conjugation, structural regulation and gene technology strategies have been demonstrated to enhance the specificity, reduce the cytotoxicity and limit the off-target cytolysis of melittin, which suggests the potential of melittin to be used clinically. This article summarizes research progress on antiviral, antitumor and anti-inflammatory properties of melittin, and discusses the strategies of melittin-modification for its future potential clinical applications in preventing drug resistance, enhancing the selectivity to target cells and alleviating cytotoxic effects to normal cells.

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Structures of calmodulin–melittin complexes show multiple binding modes lacking classical anchoring interactions

Cited by 5 publications

References 87 publications

Mobility capillary electrophoresis–native mass spectrometry reveals the dynamic conformational equilibrium of calmodulin and its complexes

Mobility capillary electrophoresis–native mass spectrometry reveals the dynamic conformational equilibrium of calmodulin and its complexes

Bee Venom: Composition and Anticancer Properties

The current landscape of the antimicrobial peptide melittin and its therapeutic potential

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