Article Metrics


Online attention

Molecular basis for GTP recognition by light‐activated guanylate cyclase RhGC

DOI: 10.1111/febs.15167 DOI Help

Authors: Agata Butryn (Diamond Light Source; Research Complex at Harwell) , Hadeeqa Raza (Diamond Light Source; Research Complex at Harwell) , Heather Rada (Protein Production UK, Research Complex at Harwell,) , Isabel Moraes (Diamond Light Source; Research Complex at Harwell) , Raymond J. Owens (Protein Production UK, Research Complex at Harwell) , Allen M. Orville (Diamond Light Source; Research Complex at Harwell)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: The Febs Journal

State: Published (Approved)
Published: December 2019
Diamond Proposal Number(s): 16818 , 19737 , 19485

Open Access Open Access

Abstract: Cyclic guanosine 3′,5′‐monophosphate (cGMP) is an intracellular signaling molecule involved in many sensory and developmental processes. Synthesis of cGMP from GTP is catalyzed by guanylate cyclase (GC) in a reaction analogous to cAMP formation by adenylate cyclase (AC). Although detailed structural information is available on the catalytic region of nucleotidyl cyclases (NCs) in various states, these atomic models do not provide a sufficient explanation for the substrate selectivity between GC and AC family members. Detailed structural information on the GC domain in its active conformation is largely missing and no crystal structure of a GTP‐bound wild‐type GC domain has been published to date. Here, we describe the crystal structure of the catalytic domain of rhodopsin‐GC (RhGC) from Catenaria anguillulae in complex with GTP at 1.7 Å resolution. Our study reveals the organization of a eukaryotic GC domain in its active conformation. We observe that the binding mode of the substrate GTP is similar to that of AC–ATP interaction, although surprisingly not all of the interactions predicted to be responsible for base recognition are present. The structure provides insights into potential mechanisms of substrate discrimination and activity regulation that may be common to all class III purine NCs.

Journal Keywords: guanylyl cyclase; cyclic GMP; cGMP; retinylidene photoreceptor

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography , VMXi-Versatile Macromolecular Crystallography in situ