Figure 1.

Open Questions in Protein Domain-Peptide Specificity

(A) Protein specificity determines the interaction between the whole kinase protein and its substrates and is driven by processes such as interactions between other domains and motifs (e.g., SH2 and phospho-tyrosine in this figure), co-expression of the two proteins, cellular localization, scaffold proteins, etc. (Bhattacharyya et al., 2006, Linding et al., 2007, Reményi et al., 2005, Scott and Pawson, 2009). Peptide specificity, in contrast, is solely driven by the sequence and structure of the kinase domain and drives the phosphorylation of specific linear motifs within the substrate protein.

(B) The so-called determinants of specificity (DoS) are those residues within a protein domain that together drive and determine the peptide specificity of the domain.

(C) While relatively few localized DoS have been described in the kinase domain, this study explores the existence of more determinants and their relative domain positions.