CONFORMATIONAL CHANGES OF SOLUBLE QUANYLATE CYCLES

Stanford University, Stanford CA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Soluble guanylate cyclase (sGC), a 150 kD heterodimeric protein, is the primary NO receptor in the cell. NO binds to heme in the N-terminal domain of the ? subunit, stimulates the production of cGMP and leads to NO-dependent signaling cascades. Structure determination has been hindered by our inability to crystallize the protein. We can prepare, in high yield, a truncated sGC (msGC-NT2, 97 kD) from the insect Manduca sexta that lacks the cyclase domain. The NO chemistry of this construct is identical to that of the full-length protein. (Hu, et.al., J. Biol. Chem., (2008), 20968.). Analytical ultracentrifugation (AUC) shows that msGC-NT2 changes shape when ligands bind. SAXS studies will further define the low resolution structure of our sGC construct and determine whether significant domain rearrangement occurs when ligands bind.