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Study · In vitro (cell-free) · 2026

5 results

Zinc Coordination by Thymosin β4: Structural Determinants and Functional Implications.

Lachowicz JI, Congiu T, Salis A, Cesare Marincola F

International journal of molecular sciences11 Feb 2026Cited by 1 (Europe PMC)

PMID41751875 (opens in a new tab)PMCIDPMC12940511 (opens in a new tab)DOI10.3390/ijms27041740 (opens in a new tab)PepBankPUB-41751875
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Summary

Thymosin β4 (Tβ4) is a highly acidic, intrinsically disordered 43-amino-acid peptide with diverse biological functions, yet its interactions with metal ions remain poorly understood. In this study, we provide the first experimental demonstration that Tβ4 forms discrete Zn2+-bound adducts and undergoes Zn2+-induced aggregation under physiological pH conditions. Combining zeta potential analysis, dynamic light scattering (DLS), electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR) spectroscopy, and scanning electron microscopy with elemental mapping (SEM/EDS), we show that Zn(II) binding progressively neutralizes Tβ4's negative surface charge and triggers a sharp aggregation transition. ESI-MS unambiguously identifies Tβ4/Zn(II) complexes of peptide-to-zinc molar ratio 1:3, while DLS and SEM reveal the formation of compact, low-solubility supramolecular assemblies. NMR measurements support a metal-induced aggregation, confirming the absence of folding upon Zn(II) binding. By quantitatively comparing the experimentally determined critical aggregation concentration with physiologically observed extracellular Zn(II) ranges, we demonstrate that aggregation is unlikely in plasma or basal interstitial environments but may become feasible in Zn-rich microdomains, such as the synaptic cleft, where transient Zn(II) levels can exceed 1 μM. These findings introduce a previously unrecognized dimension of Tβ4 chemistry and suggest that a Zn(II)-mediated supramolecular assembly of Tβ4 could influence peptide behavior in neurological or inflammatory conditions characterized by elevated extracellular Zn(II). This work establishes a foundational biochemical framework for future studies aimed at elucidating the biological implications of Tβ4/Zn(II) complexation and aggregation in vivo.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

4 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cell-free)Activity measurement

    In cell-free experiments, ESI-MS identified Tβ4/Zn(II) complexes with a peptide-to-zinc molar ratio of 1:3.

    In plain wordsIn lab tests, thymosin β4 bound zinc, with three zinc ions per peptide.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    Not applicableZn(II) adduct formation
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    ESI-MS unambiguously identifies Tβ4/Zn(II) complexes of peptide-to-zinc molar ratio 1:3
  2. 02LabIn vitro (cell-free)Activity measurement

    In cell-free experiments at physiological pH, Zn(II) triggered Tβ4 aggregation into compact, low-solubility supramolecular assemblies.

    In plain wordsIn lab tests, zinc made thymosin β4 clump together into compact assemblies that dissolve poorly.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    IncreaseZn(II)-induced aggregation
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    In this study, we provide the first experimental demonstration that Tβ4 forms discrete Zn2+-bound adducts and undergoes Zn2+-induced aggregation under physiological pH conditions.
    1 context sentence
    Summary · context
    while DLS and SEM reveal the formation of compact, low-solubility supramolecular assemblies.
  3. 03LabIn vitro (cell-free)Mechanism

    In cell-free experiments, Zn(II) binding progressively neutralized the negative surface charge of Tβ4.

    In plain wordsIn lab tests, binding zinc made the negative surface charge of thymosin β4 less negative.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    IncreaseSurface charge change on Zn(II) binding
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    we show that Zn(II) binding progressively neutralizes Tβ4's negative surface charge and triggers a sharp aggregation transition.
  4. 04LabIn vitro (cell-free)Other

    Comparing the critical aggregation concentration with physiological extracellular Zn(II) ranges, aggregation is unlikely in plasma or basal interstitial fluid but may become feasible in Zn-rich microdomains such as the synaptic cleft.

    In plain wordsLab results suggest zinc-driven clumping of thymosin β4 is unlikely in blood but could happen in zinc-rich spots such as nerve synapses.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    Not applicableFeasibility of Zn(II)-induced aggregation in physiological fluids
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    By quantitatively comparing the experimentally determined critical aggregation concentration with physiologically observed extracellular Zn(II) ranges, we demonstrate that aggregation is unlikely in plasma or basal interstitial environments but may become feasible in Zn-rich microdomains, such as the synaptic cleft, where transient Zn(II) levels can exceed 1 μM.

Studies that did not test the peptide alone1

In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Thymosin beta-4 (human).

  1. 05LabNot a test of Thymosin beta-4 (human) aloneIn vitro (cell-free)Mechanism

    In cell-free NMR measurements, Tβ4 did not fold on Zn(II) binding, which supports a metal-induced aggregation.

    In plain wordsIn lab tests, thymosin β4 stayed unfolded when it bound zinc.

    Peptide
    Thymosin beta-4 (human)
    Outcome
    No significant changeFolding on Zn(II) binding (NMR)
    Study

    n: not reported in source

    Outcome group
    Receptor activity and mechanism · Pharmacology

    Source sentences

    Summary
    NMR measurements support a metal-induced aggregation, confirming the absence of folding upon Zn(II) binding.

    In this study, Thymosin beta-4 (human) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Thymosin beta-4 (human).

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    13 Oct 2026, 01:52 UTC

    Study results updated

  2. Version 1

    12 Oct 2026, 18:17 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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