期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：50
页码：15297-15302
DOI：10.1073/pnas.1510262112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceMicrobial and animal rhodopsins share several striking structural features including a seven -helix fold and a highly conserved active-site lysine in the seventh helix. However, these protein families lack significant similarity in their amino acid sequence. In this paper we address the question of why the sequence of animal rhodopsins, featuring an 11-cis chromophore, could have diverged from a microbial ancestor incorporating the more stable all-trans chromophore. We show that, by using light-responsive computer models of a eubacterial sensory rhodopsin and of a vertebrate visual rhodopsin, it is possible to identify a distinctive electronic character of the 11-cis chromophore that could have become an effective target for natural selection. The functions of microbial and animal rhodopsins are triggered by the isomerization of their all-trans and 11-cis retinal chromophores, respectively. To lay the molecular basis driving the evolutionary transition from the all-trans to the 11-cis chromophore, multiconfigurational quantum chemistry is used to compare the isomerization mechanisms of the sensory rhodopsin from the cyanobacterium Anabaena PCC 7120 (ASR) and of the bovine rhodopsin (Rh). It is found that, despite their evolutionary distance, these eubacterial and vertebrate rhodopsins start to isomerize via distinct implementations of the same bicycle-pedal mechanism originally proposed by Warshel [Warshel A (1976) Nature 260:678-683]. However, by following the electronic structure changes of ASR (featuring the all-trans chromophore) during the isomerization, we find that ASR enters a region of degeneracy between the first and second excited states not found in Rh (featuring the 11-cis chromophore). We show that such degeneracy is modulated by the preorganized structure of the chromophore and by the position of the reactive double bond. It is argued that the optimization of the electronic properties of the chromophore, which affects the photoisomerization efficiency and the thermal isomerization barrier, provided a key factor for the emergence of the striking amino acid sequence divergence observed between the microbial and animal rhodopsins.
