Guanylyl cyclase domain structure and structure-based sequence alignment. A, domain organization of CC containing sGC and mGCs (crystallized part in purple dotted line). B, Structure-based sequence alignment of CC and adjacent regions in rat sGCβ1, sGCα1, sGCα2, Manduca sexta sGCα1 and sGCβ1, rat sGCβ2, rat GC-A, and human GC-B, GC-E, GC-F, and GC-C. Also included are Npun02000820 of Nostoc punctiforme PCC73102, labeled Np HNOXA, and the guanylyl cyclase of Chlamydomonas reinhardtii, labeled Cr GC (in grey) to indicate the proximity of the CC flanking H-NOXA and GC domains, respectively, as their structures have been determined [5, 10] (residues included in the structures are grey underlined with grey secondary structure elements). The sequence of the crystallized sGCβ1 CC is bold with red secondary structure elements. Completely conserved residues in the sGCs are highlighted green with possible conservation extending into mGCs. Mostly conserved hydrophobic residues are in yellow; mostly conserved basic residues are in blue. sGCβ1 residues 379-408 found to be important for dimerization  are black underlined. sGCβ1 residues 344-363, 381-400, and sGCα1 440-459 are important for sGC dimerization (red box); sGCβ1 401-420 and sGCα1 460-479 are important for activity but not dimerization (blue box) . The a-d designation based on the CC crystal structure A:B dimer is generated using SOCKET  and slightly extended at the (frayed) ends. CC mutations [23, 28, 40–43] are shown in a black box. Secondary structure predictions http://npsa-pbil.ibcp.fr/cgi-bin/npsa_automat.pl?page=/NPSA/npsa_seccons.html of all 7 top sequences suggested a small helix present between the H-NOXA/PAS and αA helix (black dotted lines).