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Conservation analysis and structure prediction of the SH2 family of phosphotyrosine binding domains
Author(s) -
Russell Robert B.,
Breed Jason,
Barton Geoffrey J.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)80579-6
Subject(s) - sh2 domain , protein secondary structure , amino acid , biology , peptide sequence , biochemistry , phosphotyrosine binding domain , conserved sequence , proto oncogene tyrosine protein kinase src , protein structure , binding site , phosphorylation , computational biology , chemistry , gene
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 sciences. This combined approach predicts seven core secondary structure regions with the pattern β‐α‐β‐β‐β‐β‐α, identifies those residues most likely to be buried in the hydrophobic core of the native SH2 domain, and highlights patterns of conservation indicative or 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 or the SH2 domains. Comparison of the proposed SH2 domain or ak1 to this pattern shows only matches, suggesting that this domain may not exhibit SH2‐like properties.