Tilburn Joan, Sánchez-Ferrero Juan C, Reoyo Elena, Arst Herbert N, Peñalva Miguel A
Department of Infectious Diseases, Faculty of Medicine, Imperial College London, United Kingdom.
Genetics. 2005 Sep;171(1):393-401. doi: 10.1534/genetics.105.044644. Epub 2005 Jun 8.
The alkaline ambient pH signal transduction pathway component PalC has no assigned molecular role. Therefore we attempted a gene-specific mutational analysis and obtained 55 new palC loss-of-function alleles including 24 single residue substitutions. Refined similarity searches reveal conserved PalC regions including one with convincing similarity to the BRO1 domain, denoted PCBROH, where clustering of mutational changes, including PCBROH key residue substitutions, supports its structural and/or functional importance. Since the BRO1 domain occurs in the multivesicular body (MVB) pathway protein Bro1/Vps31 and also the pH signal transduction protein PalA (Rim20), both of which interact with MVB component (ESCRT-III protein) Vps32/Snf7, this might reflect a further link between the pH response and endocytosis.
碱性环境pH信号转导途径组分PalC的分子作用尚未明确。因此,我们尝试进行基因特异性突变分析,获得了55个新的palC功能缺失等位基因,其中包括24个单残基取代。精细的相似性搜索揭示了保守的PalC区域,其中一个区域与BRO1结构域具有令人信服的相似性,称为PCBROH,包括PCBROH关键残基取代在内的突变变化聚集,支持其结构和/或功能重要性。由于BRO1结构域存在于多囊泡体(MVB)途径蛋白Bro1/Vps31以及pH信号转导蛋白PalA(Rim20)中,这两者都与MVB组分(ESCRT-III蛋白)Vps32/Snf7相互作用,这可能反映了pH反应与内吞作用之间的进一步联系。