The seven individual helices for the five GRAFS families can be aligned (except for TM2 and TM7 from the G and F families) and each helix is self-consistent across the five families, providing no evidence of reordering and the production of a different folding topology.8 Based on this remarkable degree of consistency, it is difficult to appreciate why 7TMRs are so resistant to structural elucidation attempts, assuming oligomeric complexing, coreceptors and/or other integral components are not necessary. One obvious hurdle is the purification and crystallization of a membrane protein while preserving its structural integrity. Analysis of the membraneresident protein structures that have been elucidated suggests that membrane proteins are averse to the adoption of reasonably rigid structures and that they are notoriously flexible. Indeed, flexibility of structure can be expected to help many of these membrane proteins to perform their channel, transport, flux, enzymatic, and recognition functions at the cell surface.
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