期刊
BIOCHEMISTRY
卷 46, 期 31, 页码 9133-9142出版社
AMER CHEMICAL SOC
DOI: 10.1021/bi700944j
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资金
- NHLBI NIH HHS [R01 HL056051, HL-30954, R01 HL030954-23, HL-56051, R01 HL030954, R01 HL030954-22] Funding Source: Medline
The carboxyl-terminal regions of the fibrinogen A alpha chains (alpha C regions) form compact alpha C-domains tethered to the bulk of the molecule with flexible alpha C-connectors. It was hypothesized that in fibrinogen two alpha C-domains interact intramolecularly with each other and with the central E region preferentially through its N-termini of B beta chains and that removal of fibrinopeptides A and B upon fibrin assembly results in dissociation of the alpha C regions and their switch to intermolecular interactions. To test this hypothesis, we studied the interactions of the recombinant alpha C region (A alpha 221-610 fragment) and its subfragments, alpha C-connector (A alpha 221-391) and alpha C-domain (A alpha 392-610), between each other and with the recombinant (B beta 1-66)(2) and (beta 15-66)(2) fragments and NDSK corresponding to the fibrin(ogen) central E region, using laser tweezers-based force spectroscopy. The alpha C-domain, but not the alpha C-connector, bound to NDSK, which contains fibrinopeptides A and B, and less frequently to desA-NDSK and (B beta 1-66)(2) containing only fibrinopeptides B; it was poorly reactive with desAB-NDSK and (beta 15-66)(2) both lacking fibrinopeptide B. The interactions of the alpha C-domains with each other and with the alpha C-connector were also observed, although they were weaker and heterogeneous in strength. These results provide the first direct evidence for the interaction between the alpha C-domains and the central E region through fibrinopeptide B, in agreement with the hypothesis given above, and indicate that fibrinopeptide A is also involved. They also confirm the hypothesized homomeric interactions between the alpha C-domains and display their interaction with the alpha C-connectors, which may contribute to covalent cross-linking of alpha polymers in fibrin.
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