tailieunhanh - Báo cáo Y học: Identification of novel membrane proteins by searching for patterns in hydropathy profiles

A technique has been developed to search a proteome database for new members of a functional class of membrane protein. It takes advantage of the highly conserved secondary structure of functionally related membrane proteins. Such proteins typically have the same number of transmembrane domains located at similar relative positions in their polypeptide sequence. This gives rise to a characteristic pattern of peaks in their hydropathy profiles. To conduct a search, each member of a polypeptide database is converted to a hydropathy profile, peaks are automatically detected, and the pattern of peaks is compared with a template. A template was designed. | Eur. J. Biochem. 269 2101-2107 2002 FEBS 2002 doi Identification of novel membrane proteins by searching for patterns in hydropathy profiles John D. Clements and Rowena E. Martin School of Biochemistry and Molecular Biology Australian National University Canberra Australia A technique has been developed to search a proteome database for new members of a functional class of membrane protein. It takes advantage of the highly conserved secondary structure of functionally related membrane proteins. Such proteins typically have the same number of transmembrane domains located at similar relative positions in their polypeptide sequence. This gives rise to a characteristic pattern of peaks in their hydropathy profiles. To conduct a search each member of a polypeptide database is converted to a hydropathy profile peaks are automatically detected and the pattern of peaks is compared with a template. A template was designed for the acetylcholine ACh and glycine receptors of the cys-loop receptor superfamily. The key feature was a closely spaced triplet of hydropathy peaks bracketed by deep valleys. When applied to the human proteome the search procedure retrieved 153 profiles with a receptor-like triplet of peaks. The approach was highly selective with 70 of the retrieved profiles annotated as known or putative receptors. These included ACh glycine c-amino butyric acid and seretonin receptors which are all related by sequence. However ionotropic glutamate receptors which have almost no sequence homology with ACh receptors were also retrieved. Thus the strategy can find members of a functional class that cannot be identified by sequence alignment. To demonstrate that the strategy can easily be extended to other membrane protein families a template was developed for the neurotransmitter Na symporter family and similar results were obtained. This approach should prove a useful adjunct to sequence-based retrieval tools when searching for novel .