Dominant plant resistance genes are involved in the protection of plants ag
ainst a wide variety of pathogens. Sequence analysis has revealed a variety
of classes, often having domains in common. One commonly found region has
come to be known as a putative nucleotide-binding site (NBS) due to the sim
ple presence of sequence motifs. Until now, no experimental evidence has su
pported this idea. Here we suggest, as an alternative hypothesis, that part
of this region is structurally homologous to the receiver domain common to
many proteins of His-Asp phosphotransfer pathways. This conclusion is base
d on sequence analysis, threading experiments, and the construction of a mo
lecular model of one domain that performs well against structure validation
tools. The new hypothesis, in contrast to the NBS hypothesis, can explain
the devastating effect of a Thr-->Ala mutation in a well-characterized resi
stance gene product. According to the new hypothesis, regions located N-ter
minal and C-terminal to the modeled portion, containing highly conserved se
quence motifs, could form a separate domain. Proteins 2000;41:133-143. (C)
2000 Wiley-Liss, Inc.