Premium
Versatile retargeting of SH3 domain binding by modification of non‐conserved loop residues
Author(s) -
Hiipakka Marita,
Saksela Kalle
Publication year - 2007
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/j.febslet.2007.03.044
Subject(s) - sh3 domain , computational biology , conserved sequence , biology , homology (biology) , proto oncogene tyrosine protein kinase src , chemistry , microbiology and biotechnology , genetics , peptide sequence , kinase , amino acid , gene
Src‐homology (SH3) domain belongs to a class of ubiquitous modular protein domains found in nature. SH3 domains have a conserved surface that recognises proline‐rich peptides in ligand proteins, but additional contacts also contribute to binding. Using the SH3 domain of hematopoietic cell kinase as a test case, we show that SH3 binding properties can be profoundly altered by modifications within a hexapeptide sequence in the RT‐loop region that is not involved in recognition of currently known consensus SH3 target peptides. These results highlight the role of non‐conserved regions in SH3 target selection, and introduce a strategy that may be generally feasible for generating artificial SH3 domains with desired ligand binding properties.