Conservation analysis and structure prediction of the SH2 family of phosphotyrosine binding domains.
Src homology 2 (SH2) regions are short (approximately 100 amino acids), non-catalytic domains conserved among a wide variety of proteins involved in cytoplasmic signaling induced by growth factors. It is thought that SH2 domains play an important role in the intracellular response to growth factor stimulation by binding to phosphotyrosine containing proteins. In this paper we apply the techniques of multiple sequence alignment, secondary structure prediction and conservation analysis to 67 SH2 domain amino acid sequences. This combined approach predicts seven core secondary structure regions with the pattern beta-alpha-beta-beta-beta-beta-alpha, identifies those residues most likely to be buried in the hydrophobic core of the native SH2 domain, and highlights patterns of conservation indicative of secondary structural elements. Residues likely to be involved in phosphotyrosine binding are shown and orientations of the predicted secondary structures suggested which could enable such residues to cooperate in phosphate binding. We propose a consensus pattern that encapsulates the principal conserved features of the SH2 domains. Comparison of the proposed SH2 domain of akt to this pattern shows only 12/40 matches, suggesting that this domain may not exhibit SH2-like properties.
Russell
R B
RB
University of Oxford, Laboratory of Molecular Biophysics, UK.
Breed
J
J
Barton
G J
GJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D051058:Oncogene Protein v-akt; D019000:Phosphotyrosine; D011487:Protein Conformation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry*; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry; D012689:Sequence Homology, Nucleic Acid; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D015682:Retroviridae Proteins, Oncogenic; D019000:Phosphotyrosine; D014443:Tyrosine; D016392:Proto-Oncogene Proteins pp60(c-src); D051058:Oncogene Protein v-akt