Recent mechanistic insights into conformational interconversion in metamorphic proteins.

Metamorphic proteins defy the classical Anfinsen paradigm by adopting two or more distinct native folds, each associated with unique functions, and they reversibly interconvert under physiological conditions. Recent studies have revealed that these fold-switching events are often regulated by environmental cues such as temperature, pH, and ligand binding, enabling dynamic control over protein function. In this review, we highlight recent mechanistic insights into six well-characterized metamorphic proteins-KaiB, RfaH, XCL1, ORF9b, GX A/GX B and Sa1V90T-and discuss the structural, thermodynamic, and kinetic principles underlying their fold-switching behavior. We further emphasize the emerging roles of advanced NMR techniques in mapping conformational landscapes and quantifying interconversion rates at atomic resolution. Together, these advances provide a comprehensive framework for understanding protein fold-switching as an adaptive mechanism in evolution and regulation.

• Publication year

  2026

• Venue

  International Journal of Biological Macromolecules

• Publication date

  2026-01-01

• Fields of study

  Biology, Medicine, Materials Science, Chemistry

• Identifiers
  DOI 10.1016/j.ijbiomac.2025.150007PMID 41483876
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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