Staphylococcal protein A is anchored to the cell wall, a unique cellul
ar compartment of Gram-positive bacteria. The sorting signal sufficien
t for cell wall anchoring consists of an LPXTG motif, a C-terminal hyd
rophobic domain and a charged tail. Homologous sequences are found in
many surface proteins of Gram-positive bacteria and we explored the un
iversality of these sequences to serve as cell wall sorting signals. W
e show that several signals are able to anchor fusion proteins to the
staphylococcal cell wall. Some signals do not sort effectively, but ac
quire sorting activity once the spacing between the LPXTG motif and th
e charged tail has been increased to span the same length as in protei
n A. Thus, signals for cell wall anchoring in Grain-positive bacteria
are as universal as signal (leader) sequences.