Bestrophin Structure Published
Yang and colleagues from Wayne Hendrickson‘s group at Columbia University have solved the crystal structure of a bacterial homolog of the bestrophin ion channel (KpBest) (pdb id: 4WD8). In mammals, the BEST channel family includes 4 members that encode for a Ca2+ activated, anion conducting channels.
The structure of the KpBest channel is a pentamer that includes large intersubunit contacts and a centrally-located pore. Unlike mammalian BEST channels, the KpBEST channel conducts Na+ and the surface of the pore is negatively charged.
Another difference between mammalian and bacterial BEST is in the lack of the arginine-phenylalanine-proline (RFP) signal. The RFP sequence is invariant in mammalian BEST channels and a defining feature of the channel family. Moreover, the purpose of this motif in the mammalian channel remains unknown, but appears to be located on the outer perimeter of the intracellular domains.
Left: an alignment of the sequences surrounding the RFP motif in the human BEST protein, with the expected location of the sequence in KpBEST. Middle and right: the RLL motif in KpBEST highlighted in red.
The KpBEST structure revealed two restriction sites that facilitate ion selectivity and gating respectively. The structure included striking features, such as transmembrane and cytoplasmic helical bundles with unique folds. The KpBest structure provides a basis to begin to understand human bestrophin activity and its physiological role.
Post by Hiba Al-Ashtal and Anne Carlson