Haptoglobin and the related haptoglobin protein: the N-terminus makes the difference.
J Biomol Struct Dyn
; 40(5): 2244-2253, 2022 03.
Article
en En
| MEDLINE
| ID: mdl-33103597
ABSTRACT
Haptoglobin related protein (Hpr) is a component of the trypanosome lytic factor (TLF), a complex acting in the innate immune response against African trypanosomes. Like haptoglobin (Hp), Hpr binds hemoglobin (Hb) in the blood, but unlike Hp, Hpr does not bind the CD163 receptor. Moreover, unlike Hp, Hpr retains the N-terminal signal peptide that is required for the association with Apolipoprotein L-1 (ApoL-1), a component of the TLF complex. Here, the molecular model of human Hpr has been built based on the high sequence identity with human Hp (91%). The structural bases of HprHpr dimerization and Hpr recognition by Hb and Trypanosoma brucei brucei Hp receptor (TbHpHbR) have been analyzed in parallel with those of HpHp, HpHb, and TbHpHbRHpHb complexes. We show that the Cys33-Cys33 intermolecular disulfide bridge that stabilizes the Hp1Hp1 complex is replaced by the Phe33, Pro34, and Phe48 hydrophobic core in the HprHpr dimer. Moreover, we show that the N-terminal peptide of Hpr participates in the stabilization of the HprHpr dimer. Thus, the N-terminal peptide seems to have been retained in Hpr to mediate its critical role in the human innate immunity towards Trypanosoma brucei brucei infection.Communicated by Ramaswamy H. Sarma.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trypanosoma brucei brucei
/
Haptoglobinas
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Biomol Struct Dyn
Año:
2022
Tipo del documento:
Article
País de afiliación:
Italia