Subunit interface

Figure S.21 The hemaggiutinin moiecuie is formed from three subunits. Each of these subunits Is anchored In the membrane of the influenza vims. The globular heads contain the receptor sites that bind to sialic acid residues on the surface of eukaryotic cells. A major part of the subunit interface is formed by the three long intertwining helices, one from each subunit. (Adapted from I. Wilson et al.. Nature 289 366-373, 1981.)...

Less commonly, an a-helix can be completely buried in the protein interior or completely exposed to solvent. Citrate synthase is a dimeric protein in which a-helical segments form part of the subunit-subunit interface. As shown in Figure 6.24, one of these helices (residues 260 to 270) is highly hydrophobic and contains only two polar residues, as would befit a helix in the protein core. On the other hand. Figure 6.24 also shows the solvent-exposed helix (residues 74 to 87) of cahnodulln, which consists of 10 charged residues, 2 polar residues, and only 2 nonpolar residues. 

Muscle glycogen phosphorylase is a dimer of two identical subunits (842 residues, 97.44 kD). Each subunit contains a pyridoxal phosphate cofactor, covalently linked as a Schiff base to Lys °. Each subunit contains an active site (at the center of the subunit) and an allosteric effector site near the subunit interface (Eigure 15.15). In addition, a regulatory phosphorylation site is located at Ser on each subunit. A glycogen-binding site on each subunit facilitates prior association of glycogen phosphorylase with its substrate and also exerts regulatory control on the enzymatic reaction. 

F, the EF corner, and the FG corner to follow. These shifts are transmitted to the subunit interfaces, where they trigger conformational readjustments that lead to the rupture of interchain salt links. 

Cover, J.A., Lambert, J.M., Norman, C.M., and Traut, R.R. (1981) Identification of proteins at the subunit interface of the Escherichia coli ribosome by cross-linking with dimethyl 3,3 -dithiobis(propionimi date). Biochemistry 20, 2843-2852. 

Even though the iron atoms are separated in haemoglobin by about 25 A, communication between them is still able to occur and this has been postulated to involve a trigger mechanism (Perutz, 1971). The trigger is the movement of the proximal histidine as dioxygen binds to (or is released from) the Fe(n) and results in interconversion between the T and R structures. This movement causes a conformational change which is transmitted through the protein to the other iron sites. X-ray studies indicate that relative shifts of up to 6 A at subunit interfaces occur between the T and R states (Perutz, 1978). 

Serag, A. A., Altenbach, C., Gingery, M., Hubbell, W. L., and Yeates, T. O. (2001). Identification of a subunit interface in transthyretin amyloid fibrils Evidence for self-assembly from oligomeric building blocks. Biochemistry 40, 9089-9096. 

The large and small subunits interact extensively with each other burying the catalytic site and the proximal [4Fe-4S] cluster at about 3nm from the molecular surface. It is quite remarkable that the active site and the two most buried [FeS] clusters are located close to the almost planar subunit interface. The large subunit is anchored to the small subunit by about twenty-five side chains, of which several very conserved ones interact with the proximal [4Fe-4S] cluster, pointing to the role of this cluster as a direct partner of the catalytic site. 

Bifunctional reagents have also been used to identify the ribosomal proteins present on the subunit interface on both the 30 S and 50 S subunits (Lambert and Traut, 1981 Cover et ai, 1981). Figure 12 summarizes the identified cross-linked pairs containing one protein from each subunit, suggesting that these proteins are located at the subunit interface. 

Fig. 12. Cross-linking of proteins within the E. coli (a) 30 S and (b) 50 S subunits (Traut et at., 1980). Asterisks denote proteins cross-linked to initiation factors, (c) Protein neig h-borhoods at the subunit interface (Lambert and Traut, 1981). Scheme 1 shows the crosslinks found in highest amount Scheme 2 those among 50 S proteins LI and L2 and several 30 S proteins and Scheme 3 those between 5 S RNA binding proteins and 30 S proteins. Reproduced with permission from Wittmann (1983).

A model used to explain cooperativity on the basis of ligand-induced changes in conformation that may or may not alter the subunit-subunit interfaces of oligomeric enzymes and receptors. This model has also been referred to as the Adair-Koshland-Nemethy-Filmer model (AKNF model), the induced-fit model, and the sequential model. 

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