Hinged proteins

Bovine heart cytochrome bci (PDB 1BE3 and PDB IBGY) as studied by Iwata et al. exists as a dimer in the asymmetric unit cell. Each monomer consists of 11 different polypeptide subunits (SU) with a total of -2165 amino acid residues and a molecular mass of -240 kDa. The protein subunits of the complex occupy three separate regions (1) the intermembrane space (p side) occupied by cytochrome Ci (subunit 4, SU4), the iron-sulfur protein (ISP, SU5) and subunit 8 (2) the transmembrane region occupied by cytochrome b (SU3), the transmembrane helices of cytochrome Ci and the ISP, and subunits 7,10, and 11 and (3) the matrix space (n side) occupied by two large core proteins (subunits 1 and 2) as well as subunits 6 and 9. Subunit 8 is often called the hinge protein and is thought to be essential for proper complex formation between cytochrome c (the exit point for some bci complex electrons) and... 

Lysozyme is a hinge-protein. Phillips and his coworkers describing the solid state [see The Enzymes, 3rd Ed., P. D. Boyer ed., Vol VII, Academic, New York, p. 665 (1972)] and our own solution studies both indicate that the two sides of the protein can close together when substrate is bound. The whole protein is involved in activity. It may be that other enzymes close up on binding substrates (e.g., kinases and P-450 cytochromes). 

Kim, C. H., Balny, C., and King, T. E., 1987, Role of the hinge protein in the electron transfer between cardiac cytochrome c i and c. Equilibrium constants and kinetic probes, J. Biol. Chem. 262 810388108. 

Interestingly, there are many proteins with two domains that show a very clear hinge-bending motion with an obvious functional significance. Such domains have often been reported in the literature, but were never detected on an automated basis. 

Fig. 5. Rigid-body analysis of citrate synthase, using two X-ray structures (after Hayward and Berendsen, Proteins 30 (1998) 144). The decomposition of the protein into two domains (dark gray and white) and two interconnecting regions (light gray) is shown, together with the hinge axis for the closing/opening motion between them.

G., Berendsen, H.J.C. The essential dynamics of thermolysin Confirmation of the hinge-bending motion and comparison of simulations in vacuum and water. Proteins 22 (1995) 45-54. 

The first technique is very intuitive. Out of the few proteins that could be crystallized in a number of different conformations, adenylate kinase is probably the best-studied example. By combining nine observed crystal structures and interpolating between them, a movie was constructed that visualized a hypothetical path of its hinge-bending transition (jVonrhein et al. 1995]). 

In an early study of lysozyme ([McCammon et al. 1976]), the two domains of this protein were assumed to be rigid, and the hinge-bending motion in the presence of solvent was described by the Langevin equation for a damped harmonic oscillator. The angular displacement 0 from the equilibrium position is thus governed by... 

The polypeptide chain of the lac repressor subunit is arranged in four domains (Figure 8.21) an N-terminal DNA-hinding domain with a helix-turn-helix motif, a hinge helix which binds to the minor groove of DNA, a large core domain which binds the corepressor and has a structure very similar to the periplasmic arablnose-binding protein described in Chapter 4, and finally a C-terminal a helix which is involved in tetramerization. This a helix is absent in the PurR subunit structure otherwise their structures are very similar. 

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