-
The solution structure and backbone dynamics of the fibronectin type I and epidermal growth factor-like pair of modules of tissue-type plasminogen activator.
Oxford Centre for Molecular Sciences, UK.
BACKGROUND: The thrombolytic serine protease tissue-type plasminogen activator (t-PA) is a classical modular protein consisting of three types of domain in addition to the serine protease domain: F1 (homologous to fibronectin type I); G (epidermal growth factor-like) and kringle. Biochemical data suggest that the F1 and G modules play a major role in the binding of t-PA to fibrin and to receptors on hepatocytes. RESULTS: We have derived the solution structure of the F1 and G pair of modules from t-PA by two- and three-dimensional NMR techniques, in combination with dynamical simulated annealing calculations. We have also obtained information about the molecule's backbone dynamics through measurement of amide 15N relaxation parameters. CONCLUSIONS: Although the F1 and G modules each adopt their expected tertiary structure, the modules interact intimately to bury a hydrophobic core, and the inter-module linker makes up the third strand of the G module's major beta-sheet. The new structural results allow the interpretation of earlier mutational data relevant to fibrin-binding and hepatocyte-receptor binding.
PMID: 7582899 [PubMed - indexed for MEDLINE]
-
Cited by 2 PubMed Central articles
-
A positively charged cluster in the epidermal growth factor-like domain of Factor VII-activating protease (FSAP) is essential for polyanion binding.
Altincicek B, Shibamiya A, Trusheim H, Tzima E, Niepmann M, Linder D, Preissner KT, Kanse SM.
Biochem J. 2006 Mar 15; 394(Pt 3):687-92.
[Biochem J. 2006]
-
The fifth epidermal growth factor-like domain of thrombomodulin does not have an epidermal growth factor-like disulfide bonding pattern.
White CE, Hunter MJ, Meininger DP, Garrod S, Komives EA.
Proc Natl Acad Sci U S A. 1996 Sep 17; 93(19):10177-82.
[Proc Natl Acad Sci U S A. 1996]
Structures reported by this article