Titel
Semisynthesis of segmentally isotope-labeled and site–specifically palmitoylated CD44 cytoplasmic tail
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Abstract
CD44, a ubiquitously expressed transmembrane receptor, plays a crucial role in cell growth, migration, and tumor progression. Dimerization of CD44 is a key event in signal transduction and has emerged as a potential target for anti-tumor therapies. Palmitoylation, a posttranslational modification, disrupts CD44 dimerization and promotes CD44 accumulation in ordered membrane domains. However, the effects of palmitoylation on the structure and dynamics of CD44 at atomic resolution remain poorly understood. Here, we present a semisynthetic approach combining solid-phase peptide synthesis, recombinant expression, and native chemical ligation to investigate the impact of palmitoylation on the cytoplasmic domain (residues 669-742) of CD44 (CD44ct) by NMR spectroscopy. A segmentally isotope-labeled and site-specifically palmitoylated CD44 variant enabled NMR studies, which revealed chemical shift perturbations and indicated local and long-range conformational changes induced by palmitoylation. The long-range effects suggest altered intramolecular interactions and potential modulation of membrane association patterns. Semisynthetic, palmitoylated CD44ct serves as the basis for studying CD44 clustering, conformational changes, and localization within lipid rafts, and could be used to investigate its role as a tumor suppressor and to explore its therapeutic potential.
Stichwort
Protein semisynthesisProtein lipidationSegmental isotope labelingCD44Protein NMRParamagnetic Relaxation Enhancement (PRE)Solid phase peptide synthesisNative chemical ligation
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
Erschienen in
Titel
Bioorganic & Medicinal Chemistry
ISSN
0968-0896
Erscheinungsdatum
2024
Publication
Elsevier BV
Projekt
Kod / Identifikator
LS17-008
Erscheinungsdatum
2024
Zugänglichkeit
Rechteangabe
© 2024 The Authors

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