Ni(II) stimulates innate immunity via the direct binding to human toll like receptor 4 (hTLR4), the bacterial lipopolysaccharide receptor. This interaction is specific for humans and causes nickel contact allergy. The protein sequence of hTLR4 revealed that the ectodomain, the region supposed to coordinate the metal ions, contains a histidine-rich motif that is not conserved among all organisms. To elucidate the role of each histidine on the protein–nickel binding, we investigated the Ni(II) interaction with the model peptide NH2-FQHSNRKQMSERSVFRSRRNRIYRDISHTHTR-COO-, which encompasses the sequence 429–460 of hTLR4. Potentiometric, UV–Vis, nuclear magnetic resonance and circular dichroism measurements demonstrate that the non-conserved histidine in the ectodomain cooperates in metal coordination and consequently enables the activation of the molecular mechanism involved in nickel hypersensitivity reaction.
Ni(II) interaction with a histidine-rich region of the human TLR4 protein involved in the activation of nickel contact allergy / Zoroddu, Maria Antonietta; Peana, Massimiliano Francesco; Medici, Serenella; Pelucelli, Alessio; Simula, Giancarlo; Zdyb, Karolina; Gumienna Kontecka, Elzbieta. - In: JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY. - ISSN 0946-672X. - 44:s1(2017), pp. 42-42.
Ni(II) interaction with a histidine-rich region of the human TLR4 protein involved in the activation of nickel contact allergy
ZORODDU, Maria Antonietta;PEANA, Massimiliano Francesco;MEDICI, Serenella;
2017-01-01
Abstract
Ni(II) stimulates innate immunity via the direct binding to human toll like receptor 4 (hTLR4), the bacterial lipopolysaccharide receptor. This interaction is specific for humans and causes nickel contact allergy. The protein sequence of hTLR4 revealed that the ectodomain, the region supposed to coordinate the metal ions, contains a histidine-rich motif that is not conserved among all organisms. To elucidate the role of each histidine on the protein–nickel binding, we investigated the Ni(II) interaction with the model peptide NH2-FQHSNRKQMSERSVFRSRRNRIYRDISHTHTR-COO-, which encompasses the sequence 429–460 of hTLR4. Potentiometric, UV–Vis, nuclear magnetic resonance and circular dichroism measurements demonstrate that the non-conserved histidine in the ectodomain cooperates in metal coordination and consequently enables the activation of the molecular mechanism involved in nickel hypersensitivity reaction.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.