Interplay among the “flipping” glutamine, a conserved phenylalanine, water and hydrogen bonds within a blue-light sensing LOV domain

Abstract

A combined photoacoustics and molecular dynamics approach highlights the crucial role of a conserved phenyalanine in photosensing LOV domains.

Dimeric allostery mechanism of the plant circadian clock photoreceptor ZEITLUPE

“…[50] The net result is ordering of the N/C-termini and formation of a light-dependent salt-bridge between Arg125-Glu158. We note that the observed allosteric process is directly analogous to recent computational studies of YtvA, [24] where they observed coupling between Gln conformational dynamics and light-dependent movement of a Phe residue equivalent to Phe66 (Phe46 in YtvA). These observations raise the possibility of a Gln-independent signaling PLOS COMPUTATIONAL BIOLOGY mechanism that relies on Phe movement in response to changes in flavin electronics.…”

“…The consensus model of LOV signaling involves a light-driven Gln-flip in response to changes in flavin N5 protonation. [ 11 , 16 , 17 , 24 ] In most LOV structures, the conserved Gln residue occupies a buried conformation coplanar to the flavin isoalloxazine ring. In the dark state, N5 is unprotonated, with the active site Gln forming H-bonds to the N5 and O4 positions via its amide functionality.…”

“…In the dark state, N5 is unprotonated, with the active site Gln forming H-bonds to the N5 and O4 positions via its amide functionality. [ 16 , 17 , 24 ] Upon illumination, N5 becomes protonated, leading to 180° rotation of the active site Gln to allow H-bond formation between the Gln-carbonyl group and N5-H.[ 16 , 17 , 24 ] The result is a disruption of contacts with residues in A β strand promoting conformational changes in N/C-terminal extensions to the LOV core. [ 11 , 16 ] Structures of ZTL indicate an alternative mechanism, where in the dark state Gln154 is dynamically adopting heterogeneous conformations between exposed (perpendicular to the isoalloxazine ring) and buried conformations.…”

“…iii) Evolutionary analysis revealed that the altered signaling pathway was dependent on conservation of two residues in the Aβ-strand, Gly46 and Val48, that are co-conserved in all ZTL proteins [16]. Further, examination of other LOV structures with Gly residues at the position equivalent to Gly46 revealed altered Gln dynamics in these proteins, thereby highlighting conservation of allosteric motions linking the C-terminal Gln, to N-terminal conformational changes dependent on the residue identity at position 46 in ZTL [23][24][25].…”

QM calculations predict the energetics and infrared spectra of transient glutamine isomers in LOV photoreceptors

“…Specifically, the side chain of the conserved glutamine may trigger -through a 1801 rotation after the H-transfer step -a process of structural changes by altering the hydrogen bond map of the protein. [5][6][7][8][9][10][11][12] The photocycle of LOV domains commences typically via a blue light trigger that excites the ground state flavin (S 0 ) rapidly to the singlet state (S 1 ) within femtoseconds (Fig. 2a).…”