Primary structure of Noetia ponderosa hemoglobins: Functional correlates

Homo- and heterodimeric hemoglobins have been isolated from the red cells o f the arcid clam Noetia ponderosa (Np), These hemoglobins bind oxygen coope ratively, An extensively studied dimeric hemoglobin from another arcid clam , Scapaharca inaequivalvis, exhibits a molecular mechanism for cooperative ligand binding that is radically different from tetrameric vertebrate hemog lobins, In this study, the two chains found in both Noetia hemoglobins are sequenced and compared to the hemoglobins of the related clam S, inaequival vis to determine whether Noetia hemoglobins have the structural basis for t he same unusual mechanism for cooperative ligand binding and to inquire abo ut the structural basis of absence of tetramers. Although the Noetia sequen ces are homologous to the Scapharca sequences, critical differences exist. The lack of tetramerization of Np subunits is most likely related to the ab sence of critical residues in the A and G helices that stabilize the interd imer contact seen in the Scapharca Hb tetramer, The lower affinity of the h omodimer (Np-I), but particularly the heterodimer (Np-II) with respect to t he homodimer and heterotetramer of Scapharca, can be due to (i) changes in the proximal heme environment and (ii) changes in the dimer interface. Inte ractions between Asn 100 and the heme of the other subunit are altered in N p-II due to the substitution of this residue by methionine, possibly causin g the reduced O-2 affinity of the heterodimer of Noetia, (iii) Sequence cha nges in the E and F helices present in Np-I and Np-II could also contribute to the effect through interfacial changes. In particular, the substitution of Val for Thr in position 72 is expected to have a substantial influence on the interface. We conclude that Np dimers have the structural basis for a direct heme-heme interaction mechanism for cooperativity, as in Scapharca , but there are enough sequence changes to suggest that the pathway of inte raction might be somewhat different. (C) 2000 Academic Press.