Identification of an Ordered Compact Structure within the Recombinant Bovine Fibrinogen αC-Domain Fragment by NMR

• Published in: Biochemistry (Easton) Vol. 45; no. 7; pp. 2257 - 2266
• Main Authors: Burton, Robert A, Tsurupa, Galina, Medved, Leonid, Tjandra, Nico
• Format: Journal Article
• Language: English
• Published: American Chemical Society 21.02.2006
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/bi052380c

The NMR solution structure of the bovine fibrinogen αC-domain fragment, including residues Aα374−538, reveals a type-I‘ β-hairpin, restricted at the base by a C423−C453 disulfide linkage and a short turn preceding C423. Although both faces of the hairpin are formed mainly by hydrophilic residues, one of them is uncharged while the other has a characteristic pattern of charged residues which are highly conserved among vertebrate species. Chemical shift indexing and relaxation data indicate the presence of a collapsed hydrophobic region next to the hairpin that includes approximately 30 residues with slower concerted motion and higher content of nonpolar residues and, according to a previous study (Tsurupa, G., Tsonev, L., and Medved, L. (2002) Biochemistry 41, 6449−6459), may cooperate with the hairpin to form a compact cooperative unit (domain). Structure and relaxation data show that the region between C423 and C453 is populated by both random coil and β-structure, suggesting that the cooperative structure in the isolated αC-domain is intrinsically unstable. This observation is in agreement with a very low energy of stabilization of the Aα374−538 fragment determined in unfolding experiments. The low stability of the αC-domain suggests a possible explanation for the previously observed intra- and intermolecular interactions of these domains in fibrinogen and fibrin.