The Wnt family of secreted molecules functions in cell-fate determination
and morphogenesis during development in both vertebrates and invertebrates
(reviewed in ref. 1). Drosophila Wingless
is a ...founding member of this family, and many components of its signal transduction
cascade have been identified, including the Frizzled class of receptor. But
the mechanism by which the Wingless signal is received and transduced across
the membrane is not completely understood. Here we describe a gene that is
necessary for all Wingless signalling events in Drosophila. We show
that arrow gene function is essential in cells receiving Wingless input
and that it acts upstream of Dishevelled. arrow encodes a single-pass
transmembrane protein, indicating that it may be part of a receptor complex
with Frizzled class proteins. Arrow is a low-density lipoprotein (LDL)-receptor-related
protein (LRP), strikingly homologous to murine and human LRP5 and LRP6. Thus,
our data suggests a new and conserved function for this LRP subfamily in Wingless/Wnt
signal reception.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In Escherichia coli, the ClpAP protease, together with the adaptor protein ClpS, is responsible for the degradation of proteins bearing an amino‐terminal destabilizing amino acid (N‐degron). Here, we ...determined the three‐dimensional structures of ClpS in complex with three peptides, each having a different destabilizing residue—Leu, Phe or Trp—at its N terminus. All peptides, regardless of the identity of their N‐terminal residue, are bound in a surface pocket on ClpS in a stereo‐specific manner. Several highly conserved residues in this binding pocket interact directly with the backbone of the N‐degron peptide and hence are crucial for the binding of all N‐degrons. By contrast, two hydrophobic residues define the volume of the binding pocket and influence the specificity of ClpS. Taken together, our data suggest that ClpS has been optimized for the binding and delivery of N‐degrons containing an N‐terminal Phe or Leu.
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