The unusual syndrome Wiskott-Aldrich Syndrome has been found to be linked to a mutation in a gene expressing the Wiskott-Aldrich Syndrome protein (WASp). Due to the conservation of certain mechanisms and the homologous proteins from lower to higher eukaryotes, yeast has been used to study the molecular mechanisms that underlie diseases in humans. The yeast WASp homologue, Las17p (Local Anaexthetic Sentivie 17) and the yeast homologye Vrpp of its (i.e. human WASp) partner protein known as WIP (WASp-interacting protein), have been studied with the intention to investigate the phenotypes that arise in cells deficient in Vrp1p. A protein-protein interaction is believed to occur in the absence of Vrp1p, the interaction between the SH3 domain of the yeast F-Bar protein Hof1p and the FH1 domain of the yeast formin protein Bnr1p. This interaction is thought to have pathological effects, such as inhibition of cell proliferation and other phenotypes.
This study has been conducted in an attempt to map the binding site of Hof1p SH3 domain in the Bnr1p FH1 domain more specifically, based on previous studies suggesting that Fragment 1(755-905) of Bnr1p Full Interacting Fragment(755-1375), including the proline- rich FH1 domain, interacts with Hof1p SH3 domain in cells deficient in Vrp1p. Both Hof1p and Bnr1p are involved in the cytokinesis stagemof the yeast cell cycle. The hypothesis implies that the excessive interaction of Hof1p SH3 domain and Bnr1p FH1 domain may interrupt the cytokinesis, which thereby can lead to the growth of defects.
There was no finding of binding site within the Bnr1p FH1 domain for the Hof1p SH3 domain during this study. This can be due to various reason as explained later. Even though, this study has cast some doubts on previously conducted studies.
2014. , 31 p.