Interface sliding as illustrated by the multiple quaternary structures of liganded hemoglobin

Initial crystallographic studies suggested that fully liganded mammalian he moglobin can adopt only a single quaternary structure, the quaternary R Str ucture. However, more recent crystallographic studies revealed the existenc e of a second quaternary structure for liganded hemoglobin, the quaternary R2 structure. Since these quaternary structures can be crystallized, both m ust be energetically accessible structures that coexist in solution. Unansw ered questions include (i) the relative abundance of the R and R2 structure s under various solution conditions and (ii) whether other quaternary struc tures are energetically accessible for the liganded alpha (2)beta (2) hemog lobin tetramer. Although crystallographic methods cannot directly answer th e first question, they represent the most direct and most accurate approach to answering the second question. We now have determined and refined three different crystal structures of bovine carbonmonoxyhemoglobin. These struc tures provide clear evidence that the dimer-dimer interface of liganded hem oglobin has a wide range of energetically accessible structures that are re lated to each other by a simple sliding motion. The dimer-dimer interface a cts as a "molecular slide bearing" that allows the two arp dimers to slide back and forth without greatly altering the number or the nature of the int ersubunit contacts. Since the general stereochemical features of this inter face are not unusual, it is likely that interface sliding of the kind displ ayed by fully liganded hemoglobin plays important structural and functional roles in many other protein assemblies.