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Role of the beta-strand insert in the central domain of the fibrinogen gamma-module
- Source :
- Biochemistry. 39(51)
- Publication Year :
- 2000
-
Abstract
- The crystal structure of the fibrinogen gamma-module (residues gamma143-411) [Yee, V. C., et al. (1997) Structure 5, 125-138] revealed an unusual feature. Namely, residues gamma381-390 in the functionally important COOH-terminal region form a beta-strand that is inserted into an antiparallel beta-sheet of the central domain (gamma192-286), while the rest (gamma393-411) seems to be flexible. To clarify the structural and functional importance of this beta-strand insert, we analyzed the folding status of the plasmin-derived fibrinogen fragment D(3) and several truncated variants of the gamma-module expressed in Escherichia coli. It was found that D(3), in which most of the COOH-terminal domain of the gamma-module (gamma287-379) is removed proteolytically, retains a gamma374-405 peptide that seems to be associated noncovalently with the bulk of the molecule via its beta-strand insert region. A study of the denaturation-renaturation process of D(3) suggested that without this peptide its truncated gamma-module remains folded but is destabilized. This was confirmed directly with the truncated recombinant variants of the gamma-module, including residues gamma148-392, gamma148-373, and gamma148-286. They all were folded, but those devoid of the beta-strand insert were destabilized. The results indicate that although the beta-strand insert contributes to the stabilization of the gamma-module, it can be removed without destroying the compact structure of the latter. On the basis of this finding and some other observations, we propose a mechanism for the function-related conformational changes in the fibrin(ogen) gamma-modules.
- Subjects :
- Models, Molecular
Protein Folding
Stereochemistry
Beta sheet
Peptide
Crystal structure
Antiparallel (biochemistry)
medicine.disease_cause
Fibrinogen
Biochemistry
Fibrin
Protein Structure, Secondary
law.invention
Fibrin Fibrinogen Degradation Products
Structure-Activity Relationship
law
medicine
Humans
Computer Simulation
Escherichia coli
Sequence Deletion
chemistry.chemical_classification
biology
Calorimetry, Differential Scanning
Peptide Fragments
Recombinant Proteins
Protein Structure, Tertiary
Spectrometry, Fluorescence
chemistry
biology.protein
Recombinant DNA
Chromatography, Gel
Thermodynamics
medicine.drug
Subjects
Details
- ISSN :
- 00062960
- Volume :
- 39
- Issue :
- 51
- Database :
- OpenAIRE
- Journal :
- Biochemistry
- Accession number :
- edsair.doi.dedup.....920335f52b88e305b86575c5c6549f47