1. ECK, M.J., DHE-PAGANON, S., TRUB, T., NOITE, R.T. AND SHOELSON, S.E.
Structure of the IRS-1 PTB domain bound to the juxtamembrane region of the
CELL 85 695-705 (1996).
2. ZHOU, M., HUANG, B., OLEJNICZAK, E.T., MEADOWS, R.P., SHUKER, S.B.,
MIYAZAKI, M., TRUB, T., SHOELSON, S.E. AND FESIK, S.W.
Structural basis for IL-4 receptor phosphopeptide recognition by the IRS1-1
NAT.STRUCT.BIOL. 3 388-393 (1996).
Insulin receptor substrate-1 proteins contain both a pleckstrin homology
domain and a phosphotyrosine binding (PTB) domain. These domains facilitate
interaction with the activated tyrosine-phosphorylated insulin receptor.
The PTB domain, which is situated towards the N-terminus, comprises 105
residues. Two of its arginines (Arg212 and Arg227) are responsible for
hydrogen bonding phosphotyrosine residues on a Ac-LYASSNPApY-NH2 peptide
in the juxtamembrane region of the insulin receptor. Further interactions
via `bridged' water molecules are coordinated by residues Asn210 and Ser228
The PTB domain has a compact, 7-stranded beta-sandwich structure, capped by
a C-terminal helix. The substrate peptide fits into an L-shaped surface
cleft formed from the C-terminal helix and strands 5 and 6 .
INSULINRSI is a 6-element fingerprint that provides a signature for the
insulin receptor substrate-1 PTB domain. The fingerprint was derived from
an initial alignment of 6 sequences: motif 1 includes the first beta-strand;
motif 2 spans strands 2 and 3; motif 3 spans strands 4 and 5; motifs 4 and
5 include strands 6 and 7 res.; and motif 6 spans the alpha-helix. A single
iteration of OWL28.3 was required to reach convergence, no further sequences
being identified beyond the starting set. A single partial match was also
found, XLU27842, a C-terminal fragment that lacks motifs 1-3.
An update on SPTR37_9f identified a true set of 8 sequences, and 1