Towards an accurate alignment of G-protein-coupled receptors from different classes.

G-protein coupled receptors (GPCRs) are a large and diverse family of cell surface receptors involved in signal transduction. They share a general structure of a seven transmembrane domain, an extracellular N-terminus and an intracellular C-terminus domain responsible for coupling to the G-protein. GPCRs are split into 6 families (class A to F) based on sequence homology. GPCRs are associated with a number of diseases such as Schizophrenia, Parkinson’s, Alzheimer’s, anxiety and some cancers making them attractive targets for drug design. There is huge potential for further development of drugs that target GPCRs and the more that is understood about the receptors and their structures, the better the chance of discovering a successful drug compound. An accurate way to model the structure of other GPCRs using known structures from X-ray crystallography would, therefore, be very useful. To do this, sequences from the different classes of GPCR will need to be aligned as accurately as possible. Half sphere exposure data can be used to more accurately identify the transmembrane regions which are the most conserved across the different classes. The method used then compared ungapped alignments of defined helical regions. An ungapped pair-wise alignment was carried out to compare two helix sequences at a time (one from class C and the other from class A, B, E or F) and to score how well they align at each position. This data was then collected, each top scoring alignment from the pair-wise alignments is noted and the alignment that has the highest number of votes is considered to be the best. The criteria that were scored at each alignment were the BLOSUM matrix scores, hydropathy, entropy, amino acid volume and variability.

Level dc:type.qualificationlevel

masters

Grantor dc:publisher.institution

University of Essex

Year dc:date.issued

2017

Author dc:creator

• Farr, Joanna

• Q Science (General)
• QH301 Biology

Language dc:language

en