Dynamical Oligomerisation of Histidine Rich Intrinsically Disordered Proteins Is Regulated through Zinc-Histidine Interactions
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Dynamical Oligomerisation of Histidine Rich Intrinsically Disordered Proteins Is Regulated through Zinc-Histidine Interactions. / Cragnell, Carolina; Staby, Lasse; Lenton, Samuel; Kragelund, Birthe B.; Skepö, Marie.
I: Biomolecules, Bind 9, Nr. 5, 168, 2019.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Dynamical Oligomerisation of Histidine Rich Intrinsically Disordered Proteins Is Regulated through Zinc-Histidine Interactions
AU - Cragnell, Carolina
AU - Staby, Lasse
AU - Lenton, Samuel
AU - Kragelund, Birthe B.
AU - Skepö, Marie
PY - 2019
Y1 - 2019
N2 - Intrinsically disordered proteins (IDPs) can form functional oligomers and in some cases, insoluble disease related aggregates. It is therefore vital to understand processes and mechanisms that control pathway distribution. Divalent cations including Zn2+ can initiate IDP oligomerisation through the interaction with histidine residues but the mechanisms of doing so are far from understood. Here we apply a multi-disciplinary approach using small angle X-ray scattering, nuclear magnetic resonance spectroscopy, calorimetry and computations to show that that saliva protein Histatin 5 forms highly dynamic oligomers in the presence of Zn2+. The process is critically dependent upon interaction between Zn2+ ions and distinct histidine rich binding motifs which allows for thermodynamic switching between states. We propose a molecular mechanism of oligomerisation, which may be generally applicable to other histidine rich IDPs. Finally, as Histatin 5 is an important saliva component, we suggest that Zn2+ induced oligomerisation may be crucial for maintaining saliva homeostasis.
AB - Intrinsically disordered proteins (IDPs) can form functional oligomers and in some cases, insoluble disease related aggregates. It is therefore vital to understand processes and mechanisms that control pathway distribution. Divalent cations including Zn2+ can initiate IDP oligomerisation through the interaction with histidine residues but the mechanisms of doing so are far from understood. Here we apply a multi-disciplinary approach using small angle X-ray scattering, nuclear magnetic resonance spectroscopy, calorimetry and computations to show that that saliva protein Histatin 5 forms highly dynamic oligomers in the presence of Zn2+. The process is critically dependent upon interaction between Zn2+ ions and distinct histidine rich binding motifs which allows for thermodynamic switching between states. We propose a molecular mechanism of oligomerisation, which may be generally applicable to other histidine rich IDPs. Finally, as Histatin 5 is an important saliva component, we suggest that Zn2+ induced oligomerisation may be crucial for maintaining saliva homeostasis.
U2 - 10.3390/biom9050168
DO - 10.3390/biom9050168
M3 - Journal article
C2 - 31052346
VL - 9
JO - Biomolecules
JF - Biomolecules
SN - 2218-273X
IS - 5
M1 - 168
ER -
ID: 225279246