Abstract. The src homology region 3 (SH3) domainbearing protein Bemlp and the Rho-type GTPase Cdc42p are important for bud emergence in Saccharomyces cerevisiae. Here, we present evidence that through its second SH3 domain, Bemlp binds to the structurally and functionally similar proteins Boilp and Boi2p, each of which contain an SH3 and a pleckstrin homology (PH) domain. Deletion of BOll and BOI2 together leads to impaired morphogenesis and poor viability. A PH domain-bearing segment of Boilp that lacks the Bemlp-binding site is necessary and sufficient for function. This segment of Boilp displays a twohybrid interaction with Cdc42p, suggesting that Boilp either binds directly to or is part of a larger complex that contains Cdc42p. Consistent with these possibilities, overexpression of Boilp inhibits bud emergence, but this inhibition is counteracted by cooverexpression of Cdc42p. Increased expression of the Rho-type GTPase Rho3p, which is implicated in bud growth, suppresses the growth defects of boil boi2 mutants, suggesting that Boilp and Boi2p may also play roles in the activation or function of Rho3p. These findings provide an example of a tight coupling in function between PH domain-bearing proteins and both Rho-type GTPases and SH3 domain-containing proteins, and they raise the possibility that Boilp and Boi2p play a role in linking the actions of Cdc42p and Rho3p.T HE src homology region 3 (SH3) 1 and pleckstrin homology (PH) domains are present in many proteins that are involved in signal transduction and the organization of the cortical cytoskeleton (Pawson, 1995). The binding sites for SH3 domains generally appear to be short, proline-rich sequences . Less is known about the binding sites for PH domains. The findings that the PH domains in some proteins overlap with sequences that can bind to the 13y subunit of some trimeric G proteins (Touhara et al., 1994) and that some PH domains can bind PIP2 (Harlan et al., 1994), however, raise the possibility that a general role of PH domains might be to target proteins to membranes.Rho-type GTPases also are involved in signal transduction and the organization of the cortical cytoskeleton
This paper introduces hyper-ellipsoids as an improvement to hyper-spheres as intrusion detectors in a negative selection problem within an artificial immune system. Since hyper-spheres are a specialization of hyper-ellipsoids, hyperellipsoids retain the benefits of hyper-spheres. However, hyper-ellipsoids are much more flexible, mostly in that they can be stretched and reoriented. The viability of using hyper-ellipsoids is established using several pedagogical problems. We conjecture that fewer hyper-ellipsoids than hyperspheres are needed to achieve similar coverage of nonself space in a negative selection problem. Experimentation validates this conjecture. In pedagogical benchmark problems, the number of hyper-ellipsoids to achieve good results is significantly ( 50%) smaller than the associated number of hyper-spheres.
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