Roles of Conserved Residues Functional and Structural

Some Conserved Residues and Sequence-Structure Relationship in GlpFa h 

Four of the group III residues are conserved glycines located within helices. Far from any more usual role in disrupting helices of soluble proteins, these transmembrane helix glycines allow the closest approach in the helical bundle (Javadpour et al., 1999) that occurs in the central plane. These glycines are invariant or highly conserved to fulfil their role in the close contacts at the helix crossing contacts (MacKenzie etal., 1997). 

The helices diverge outward from this central plane of closest contact to generate the vestibules, one on on each surface. The interhelix angles of +35° to +40° are not in the categories most favored by knobs into 

The two conserved, buried glutamates Glu-14, Glu-152 have clear functional roles, each orienting four carbonyls of successive amino acids in the vestibules. The conserved pair of group III Gly-64 and Gly-199 are symmetrically located at the extremities of the central selective filter and serve to structure the downturn of the extended chains from 65 to 68 and 200 to 203 that form the critical line of four carbonyls each that in turn provide the pitons for successive hydrogen bond donors on their way through the channel (Fig. 3). 

The conservation of the -NPA- sequences at 68—70 and 203—205 can be rationalized in both structural and functional terms. Structurally it preserves a key signature contact between M3 and M7. There are plausible structural reasons why residues that are in contact around the quasi twofold axis such as the pair of NPA motifs and the Gly-49, Gly-184 pair would remain conserved, since each effectively resolves two packing situations at once. All these residues related by the quasi twofold within GlpF are among the most conserved residues throughout the entire AQP protein family. This therefore suggests that the GlpF structure is prophetic of all other AQP relatives. 

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