Biomedical subjects

M Overduin

Publications and source records attributed to M Overduin.

22 records · Page 2Linked to original sources

PubMed1994

Purification and spectroscopic characterization of a recombinant amino-terminal polypeptide fragment of mouse epithelial cadherin.

Cadherins are a family of Ca(2+)-dependent cell adhesion molecules containing four extracellular tandem repeats each of 110 amino acids. The most amino-terminal repeat is believed to confer the specificity of cell adhesion. A polypeptide containing the amino-terminal repeat of mouse epithelial cadherin has been over-expressed in E. coli and purified to homogeneity. This polypeptide binds Ca2+ with a dissociation constant of 1.6 x 10(-4) M. CD and NMR experiments indicate that the polypeptide adopts a predominantly beta-sheet conformation and that binding of Ca2+ induces only small conformational changes.

Amino Acid Sequence↗

PubMed1992

Secondary structure of Src homology 2 domain of c-Abl by heteronuclear NMR spectroscopy in solution.

The Src homology 2 (SH2) domain is a recognition motif thought to mediate the association of the cytoplasmic proteins involved in signal transduction by binding to phosphotyrosyl-containing sequences in proteins. Assignments of nearly all 1H and 15N resonances of the SH2 domain from the c-Abl protein-tyrosine kinase have been obtained from homonuclear and heteronuclear NMR experiments. The secondary structure has been elucidated from the pattern of nuclear Overhauser effects, from vicinal coupling constants, and from observation of slowly exchanging amino hydrogens. The secondary structure contains two alpha-helices and eight beta-strands, six of which are arranged in two contiguous, antiparallel beta-sheets. Residues believed to be involved in phosphotyrosyl ligand binding are on a face of one beta-sheet. The alignment of homologous sequences on the basis of secondary structure suggests a conserved global fold in a family of SH2 domains.

Amino Acid Sequence↗

PubMed1992

Three-dimensional solution structure of the src homology 2 domain of c-abl.

SH2 regions are protein motifs capable of binding target protein sequences that contain a phosphotyrosine. The solution structure of the abl SH2 product, a protein of 109 residues and 12.1 kd, has been determined by multidimensional nuclear magnetic resonance spectroscopy. It is a compact spherical domain with a pair of three-stranded antiparallel beta sheets and a C-terminal alpha helix enclosing the hydrophobic core. Three arginines project from a short N-terminal alpha helix and one beta sheet into the putative phosphotyrosine-binding site, which lies on a face distal from the termini. Comparison with other SH2 sequences supports a common global fold and mode of phosphotyrosine binding for this family.

Amino Acid Sequence↗

PubMed1992

Crystal structure of the phosphotyrosine recognition domain SH2 of v-src complexed with tyrosine-phosphorylated peptides.

Three-dimensional structures of complexes of the SH2 domain of the v-src oncogene product with two phosphotyrosyl peptides have been determined by X-ray crystallography at resolutions of 1.5 and 2.0 A, respectively. A central antiparallel beta-sheet in the structure is flanked by two alpha-helices, with peptide binding mediated by the sheet, intervening loops and one of the helices. The specific recognition of phosphotyrosine involves amino-aromatic interactions between lysine and arginine side chains and the ring system in addition to hydrogen-bonding interactions with the phosphate.

Amino Acid Sequence↗