Details

Autor(en) / Beteiligte

• Rajagopalan, Lavanya
• Pereira, Fred A
• Lichtarge, Olivier
• Brownell, William E

Titel

Identification of functionally important residues/domains in membrane proteins using an evolutionary approach coupled with systematic mutational analysis

Ist Teil von

• Methods in molecular biology (Clifton, N.J.), 2009, Vol.493, p.287

Ort / Verlag

United States

Erscheinungsjahr

2009

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Structure-function studies of membrane proteins present a unique challenge to researchers due to the numerous technical difficulties associated with their expression, purification and structural characterization. In the absence of structural information, rational identification of putative functionally important residues/regions is difficult. Phylogenetic relationships could provide valuable information about the functional significance of a particular residue or region of a membrane protein. Evolutionary Trace (ET) analysis is a method developed to utilize this phylogenetic information to predict functional sites in proteins. In this method, residues are ranked according to conservation or divergence through evolution, based on the hypothesis that mutations at key positions should coincide with functional evolutionary divergences. This information can be used as the basis for a systematic mutational analysis of identified residues, leading to the identification of functionally important residues and/or domains in membrane proteins, in the absence of structural information apart from the primary amino acid sequence. This approach is potentially useful in the context of the auditory system, as several key processes in audition involve the action of membrane proteins, many of which are novel and not well characterized structurally or functionally to date.