Evolutionary and Functional Relationships in the Truncated Hemoglobin Family.

JUAN PABLO BUSTAMANTE; LEANDRO RADUSKY; LEONARDO BOECHI; DARIO A ESTRIN; ARJEN TEN HAVE; MARCELO A MARTI

PLOS COMPUTATIONAL BIOLOGY

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2016

1553-734X

Predicting function from sequence is an important goal in current biological research, andalthough, broad functional assignment is possible when a protein is assigned to a family,predicting functional specificity with accuracy is not straightforward. If function is providedby key structural properties and the relevant properties can be computed using thesequence as the starting point, it should in principle be possible to predict function in detail.The truncated hemoglobin family presents an interesting benchmark study due to their ubiq-uity, sequence diversity in the context of a conserved fold and the number of characterizedmembers. Their functions are tightly related to O 2 affinity and reactivity, as determined bythe association and dissociation rate constants, both of which can be predicted and ana-lyzed using in-silico based tools. In the present work we have applied a strategy, whichcombines homology modeling with molecular based energy calculations, to predict andanalyze function of all known truncated hemoglobins in an evolutionary context. Our resultsshow that truncated hemoglobins present conserved family features, but that its structure isflexible enough to allow the switch from high to low affinity in a few evolutionary steps. Mostproteins display moderate to high oxygen affinities and multiple ligand migration paths,which, besides some minor trends, show heterogeneous distributions throughout the phylo-genetic tree, again suggesting fast functional adaptation. Our data not only deepens ourcomprehension of the structural basis governing ligand affinity, but they also highlight someinteresting functional evolutionary trends