Histidiinistä

J Biol Chem. 2011 Jul 8. [Epub ahead of print] Histidine-rich glycoprotein binds fibrin(ogen) with high affinity and competes with thrombin for binding to the {gamma} '-chain.

Vu TT, Stafford AR, Leslie BA, Kim PY, Fredenburgh JC, Weitz JI.

Source

McMaster University, Canada.

Abstract

Histidine-rich glycoprotein (HRG) is an abundant protein that binds fibrinogen and other plasma proteins in a Zn(2+)-dependent fashion, but whose function is unclear. HRG has antimicrobial activity and its incorporation into fibrin clots facilitates bacterial entrapment and killing and promotes inflammation. Although these findings suggest that HRG contributes to innate immunity and inflammation, little is known about the HRG/fibrin(ogen) interaction. By immunoassay, HRG-fibrinogen complexes were detected in Zn(2+)-supplemented human plasma, a finding consistent with a high affinity interaction. Surface plasmon resonance (SPR) determinations support this concept and show that in the presence of Zn(2+), HRG binds the predominant γ(A)/γ(A)-fibrinogen, and the γ-chain elongated isoform, γ(A)/γ(')-fibrinogen, with Kd values of 9 nM. Likewise, (125)I-labeled HRG binds γ(A)/γ(A)- or γ(A)/γ(')-fibrin clots with similar Kd values when Zn(2+) is present. There are multiple HRG binding sites on fibrin(ogen) because HRG binds immobilized fragment D or E of fibrinogen and γ(')-peptide, an analog of the COOH-terminus of the γ(')-chain that mediates the high affinity interaction of thrombin with γ(A)/γ(')-fibrin. Thrombin competes with HRG for γ(')-peptide binding and displaces (125)I-HRG from γ(A)/γ(')-fibrin clots and vice versa. Taken together, these data suggest that (a) HRG circulates in complex with fibrinogen and that the complex persists upon fibrin formation, and (b) by competing with thrombin for γ(A)/γ(')-fibrin binding, HRG may modulate coagulation. Therefore, the HRG-fibrin interaction may provide a novel link between coagulation, innate immunity and inflammation.

PMID:

21757718

[PubMed - as supplied by publisher]

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huom. Malariaplasmodilla on  sekvenssi, jossa on  histidiininpitoisen glykoproteiinin sekvenssiéjä. 
Ihmisen verenkierron  proteiini HRG suojaa malariaplasmodien rosetin muodostukselta. 
Mutta silloin pitäisi ravitsemuksellisen histidiinin tosiaankin olla riittävä. Yleensä malariaa saa  aliravitsemuksessa olevat. kansat eniten maan päällä.