TY  - JOUR
AU  - Schmidt, H.
AU  - Hoffmann, S.
AU  - Tran, T.
AU  - Stoldt, M.
AU  - Stangler, T.
AU  - Wiesehan, K.
AU  - Willbold, D.
TI  - Solution structure of a Hck SH3 domain ligand complex reveals novel interaction modes
JO  - Journal of molecular biology
VL  - 365
SN  - 0022-2836
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - PreJuSER-55440
SP  - 1517 - 1532
PY  - 2007
N1  - Record converted from VDB: 12.11.2012
AB  - We studied the interaction of hematopoietic cell kinase SH3 domain (HckSH3) with an artificial 12-residue proline-rich peptide PD1 (HSKYPLPPLPSL) identified as high affinity ligand (K(D)=0.2 muM). PD1 shows an unusual ligand sequence for SH3 binding in type I orientation because it lacks the typical basic anchor residue at position P(-3), but instead has a tyrosine residue at this position. A basic lysine residue, however, is present at position P(-4). The solution structure of the HckSH3:PD1 complex, which is the first HckSH3 complex structure available, clearly reveals that the P(-3) tyrosine residue of PD1 does not take the position of the typical anchor residue but rather forms additional van der Waals interactions with the HckSH3 RT loop. Instead, lysine at position P(-4) of PD1 substitutes the function of the P(-3) anchor residue. This finding expands the well known ligand consensus sequence +xxPpxP by +xxxPpxP. Thus, software tools like iSPOT fail to identify PD1 as a high-affinity HckSH3 ligand so far. In addition, a short antiparallel beta-sheet in the RT loop of HckSH3 is observed upon PD1 binding. The structure of the HckSH3:PD1 complex reveals novel features of SH3 ligand binding and yields new insights into the structural basics of SH3-ligand interactions. Consequences for computational prediction tools adressing SH3-ligand interactions as well as the biological relevance of our findings are discussed.
KW  - Amides
KW  - Amino Acid Sequence
KW  - Binding Sites
KW  - Deuterium Oxide: metabolism
KW  - Half-Life
KW  - Humans
KW  - Kinetics
KW  - Ligands
KW  - Models, Molecular
KW  - Molecular Sequence Data
KW  - Nuclear Magnetic Resonance, Biomolecular
KW  - Peptide Mapping
KW  - Peptides: chemistry
KW  - Peptides: metabolism
KW  - Protein Binding
KW  - Proto-Oncogene Proteins c-hck: analysis
KW  - Proto-Oncogene Proteins c-hck: chemistry
KW  - Proto-Oncogene Proteins c-hck: metabolism
KW  - Protons
KW  - Solutions
KW  - Water: metabolism
KW  - src Homology Domains
KW  - Amides (NLM Chemicals)
KW  - Ligands (NLM Chemicals)
KW  - Peptides (NLM Chemicals)
KW  - Protons (NLM Chemicals)
KW  - Solutions (NLM Chemicals)
KW  - Water (NLM Chemicals)
KW  - Deuterium Oxide (NLM Chemicals)
KW  - HCK protein, human (NLM Chemicals)
KW  - Proto-Oncogene Proteins c-hck (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:17141806
UR  - <Go to ISI:>//WOS:000243749600023
DO  - DOI:10.1016/j.jmb.2006.11.013
UR  - https://juser.fz-juelich.de/record/55440
ER  -