Domain structure, stability and interactions in streptokinase.


The structural organization of streptokinase was established through detailed study of its denaturation by differential scanning calorimetry. Streptokinase exhibited a complex endotherm whose shape was sensitive to changing pH. In all cases the endotherms were easily described by four two-state transitions indicating unambiguously the presence of four independently folded domains in the molecule. Two of them were slightly destabilized by lowering pH from 7.0 to 3.8 while the other two were stabilized in this pH range. Two proteolytic fragments of streptokinase were examined, a 37-kDa fragment beginning at Ile1 with a cleavage following Phe62, and a 17-kDa fragment beginning at Lys 147. At pH 8.5, three two-state transitions were observed in the former and two in the latter indicating this many domains in each and suggesting that the fragments are formed by a step-wise removal of individual domains from the parent molecule. Comparison of the melting of these fragments with that of streptokinase allowed the first two transitions in the parent protein to be assigned to the melting of two NH2-terminal domains and the two higher-temperature transitions to the melting of the two COOH-terminal domains. The latter two domains strongly interact with each other since the absence of the most stable extreme COOH-terminal domain in both fragments resulted in a strong destabilization of its neighbor whose melting occurred with a midpoint near room temperature. The two NH2-terminal domains seem to be more independent. One of them melts similarly in the parent protein and both fragments while the other, formed by the 1-146 region, is less stable in the 37-kDa fragment. This destabilization is most probably due to the cleavage after Phe62 which, based on the sequence similarity of streptokinase with serine proteases, may be part of a surface-oriented loop. Study holds ProTherm entries: 7178, 7179, 7180, 7181, 7182, 7183, 7184, 7185, 7186, 7187, 7188, 7189, 7190, 7191, 7192, 7193, 7194, 7195, 7196, 7197, 7198, 7199, 7200, 7201, 7202, 7203, 7204, 7205, 7206, 7207, 7208, 7209, 7210, 7211, 7212, 7213, 7214, 7215, 7216, 7217, 7218 Extra Details: transition 1 streptokinase; fragments; domains; denaturation;,scanning calorimetry

Submission Details


Submitter: Connie Wang

Submission Date: April 24, 2018, 8:33 p.m.

Version: 1

Publication Details
Medved LV;Solovjov DA;Ingham KC,Eur. J. Biochem. (1996) Domain structure, stability and interactions in streptokinase. PMID:8706737
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
100.0 Streptokinase C P00779 STRP_STREQ
98.2 Streptokinase C P10519 STRP_STRS1
90.6 Streptokinase C P10520 STRP_STRP1