𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Stability and folding of the SH3 domain of bruton's tyrosine kinase

✍ Scribed by Chen, Ya-Juan; Lin, Shih-Chieh; Tzeng, Shiou-Ru; Patel, Himatkumar V.; Lyu, Ping-Chiang; Cheng, Jya-Wei

Publisher
John Wiley and Sons
Year
1996
Tongue
English
Weight
632 KB
Volume
26
Category
Article
ISSN
0887-3585

No coin nor oath required. For personal study only.

✦ Synopsis

Bruton's tyrosine kinase (BTK) plays an important role in B cell development. Deletion of C-terminal14 amino acids of the SH3 domain of BTK results in X-linked a g ammaglobulinemia ( X U ) , an inherited disease. We report here on the stability and folding of SH3 domain of BTK. Peptides corresponding to residues 216273 (58 residues) and 216259 (44 residues) of BTK SH3 domain were synthesized by solid phase methods; the first peptide constitutes the entire SH3 domain of BTK while the latter peptide lacks 14 amino acid residues of the C-terminal. The 58 amino acid peptide forms mainly a p-barrel type folding unit. Although small and lacking disulfide bonds, this peptide is extremely stable to thermal denaturation. Based on circular dichroism measurements, its melting temperature was found to be high, 82°C at pH 6.0. However, the Gibbs free energy (AGHzO) of the intrinsic stability and thermodynamic spontaneity of unfolding were found to be low, 2.6 kcaVmol by GdnHC1 denaturation experiments, as compared to 12 kcaVmol obtained for larger single domain proteins, indicating poor stability of SH3 domain. Addition of 500 mM of Na,SO, increased the free energy change AGHaO to 4.0 kcdmol, suggesting an ionic strength effect. The truncated peptide fails to fold correctly and adopts random coil conformation in contrast to 58 amino acid P-barrel peptide, which exhibits high thermal stability but normal or low stability at ambient temperature. These results, to our knowledge the first to delineate the importance of C-terminal in structural integrity of SH3 domains, indicate also that improper folding and/or poor stability of mutant SH3 domain in BTK likely causes X U . Proteins 26465471

📜 SIMILAR VOLUMES

SH3 domain of Bruton's tyrosine kinase c
SH3 domain of Bruton's tyrosine kinase can bind to proline-rich peptides of TH domain of the kinase and p120cbl
✍ Himatkumar V. Patel; Shiou-Ru Tzeng; Chen-Yee Liao; Shi-Han Chen; Jya-Wei Cheng 📂 Article 📅 1997 🏛 John Wiley and Sons 🌐 English ⚖ 115 KB

X-linked agammaglobulinemia (XLA), an inherited disease, is caused by mutations in the Bruton's tyrosine kinase (BTK). The absence of functional BTK leads to failure of B-cell differentiation; this incapacitates antibody production in XLA patients, who suffer from recurrent, sometimes lethal, bacter

The SH3 domain of Bruton's tyrosine kina
The SH3 domain of Bruton's tyrosine kinase displays altered ligand binding properties when auto-phosphorylated in vitro
✍ Lucy MacCarthy Morrogh; Steve Hinshelwood; Patrick Costello; Giles O. C. Cory; C 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 English ⚖ 189 KB

Btk is a member of the Tec family of protein tyrosine kinases expressed in B cells. It is stimulated following cross-linking of the B cell receptor which leads to the autophosphorylation of a specific residue in the SH3 domain, Y223. Previous work using Btk-derived fusion proteins has shown that the

Redistribution of Bruton's tyrosine kina
Redistribution of Bruton's tyrosine kinase by activation of phosphatidylinositol 3-kinase and Rho-family GTPases
✍ Beston F. Nore; Leonardo Vargas; Abdalla J. Mohamed; Lars J. Brandén; Carl-Magnu 📂 Article 📅 2000 🏛 John Wiley and Sons 🌐 English ⚖ 504 KB

Bruton's tyrosine kinase (Btk) is a member of the Tec family of protein tyrosine kinases (PTK) characterized by an N-terminal pleckstrin homology domain (PH) thought to directly interact with phosphoinositides. We report here that wild-type (wt) and also a gain-of-function mutant of Btk are redistri

Molecular analysis of Bruton’s tyrosine
Molecular analysis of Bruton’s tyrosine kinase gene in Spain
✍ Ma Cruz García Rodríguez; Eduardo López Granados; Antonio Ferreira Cerdán; Gumer 📂 Article 📅 2001 🏛 John Wiley and Sons 🌐 English ⚖ 36 KB

Mutations in Bruton´s tyrosine kinase (BTK) gene result in X linked agammaglobulinemia (XLA). Using Single Strand Conformation Polymorphism (SSCP) followed by direct sequencing 21 mutations were found in 27 patients with an XLA phenotype from 21 unrelated families. We identified 13 novel and 8 known