2P08

Structure of the N-terminally truncated PAS domain of signal transduction histidine kinase from Nostoc punctiforme PCC 73102 with homology to the H-NOXA/H-NOBA domain of the soluble guanylyl cyclase

Summary for 2P08

• Entry DOI: 10.2210/pdb2p08/pdb
• Related: 2P04
• Descriptor: signal transduction histidine kinase, SULFATE ION (3 entities in total)
• Functional Keywords: pas-like domain, homologous to domain in soluble guanylyl cyclase, transferase
• Biological source: Nostoc punctiforme
• Total number of polymer chains: 2
• Total formula weight: 26697.16

Authors

van den Akker, F.,Ma, X. (deposition date: 2007-02-28, release date: 2007-11-13, Last modification date: 2024-02-21)

Primary citation

Ma, X.,Sayed, N.,Baskaran, P.,Beuve, A.,van den Akker, F.
PAS-mediated dimerization of soluble guanylyl cyclase revealed by signal transduction histidine kinase domain crystal structure.
J.Biol.Chem., 283:1167-1178, 2008

PubMed Abstract: Signal transduction histidine kinases (STHK) are key for sensing environmental stresses, crucial for cell survival, and attain their sensing ability using small molecule binding domains. The N-terminal domain in an STHK from Nostoc punctiforme is of unknown function yet is homologous to the central region in soluble guanylyl cyclase (sGC), the main receptor for nitric oxide (NO). This domain is termed H-NOXA (or H-NOBA) because it is often associated with the heme-nitric oxide/oxygen binding (H-NOX) domain. A structure-function approach was taken to investigate the role of H-NOXA in STHK and sGC. We report the 2.1 A resolution crystal structure of the dimerized H-NOXA domain of STHK, which reveals a Per-Arnt-Sim (PAS) fold. The H-NOXA monomers dimerize in a parallel arrangement juxtaposing their N-terminal helices and preceding residues. Such PAS dimerization is similar to that previously observed for EcDOS, AvNifL, and RmFixL. Deletion of 7 N-terminal residues affected dimer organization. Alanine scanning mutagenesis in sGC indicates that the H-NOXA domains of sGC could adopt a similar dimer organization. Although most putative interface mutations did decrease sGCbeta1 H-NOXA homodimerization, heterodimerization of full-length heterodimeric sGC was mostly unaffected, likely due to the additional dimerization contacts of sGC in the coiled-coil and catalytic domains. Exceptions are mutations sGCalpha1 F285A and sGCbeta1 F217A, which each caused a drastic drop in NO stimulated activity, and mutations sGCalpha1 Q368A and sGCbeta1 Q309A, which resulted in both a complete lack of activity and heterodimerization. Our structural and mutational results provide new insights into sGC and STHK dimerization and overall architecture.

PubMed: 18006497
DOI: 10.1074/jbc.M706218200

Experimental method

X-RAY DIFFRACTION (2 Å)