Proteins knobs

Detailed structure determinations of GCN4 and other coiled-coil proteins have shown that the a helices pack against each other according to the "knobs in holes" model first suggested by Francis Crick (Figure 3.5). Each side chain in the hydrophobic region of one of the a helices can contact four side chains from the second a helix. The side chain of a residue in position "d"... 

In most four-helix bundle structures, including those shown in Figure 3.7, the a helices are packed against each other according to the "ridges in grooves" model discussed later in this chapter. However, there are also examples where coiled-coil dimers packed by the "knobs in holes" model participate in four-helix bundle structures. A particularly simple illustrative example is the Rop protein, a small RNA-binding protein that is encoded by certain plasmids and is involved in plasmid replication. The monomeric sub unit of Rop is a polypeptide chain of 63 amino acids built up from two... 

KNOB protein, however, was shown to improve gene expression markedly (130-fold in HeLa cells). Additionally, it was shown that PEG could be conjugated to the surface of the nanospheres to prevent aggregation during lyophilization without a loss of bioactivity following one month in storage. The PEGylated particles, however, were cleared from mice at a slower rate than unmodified controls and were found to accumulate in the kidney and liver at 15 min after intravenous administration. There was no difference after one hour, however. 

Each coat subunit in the Ff viruses is coiled into an a-helical rod of 7 nm length. These are arranged in the virus in a right-handed helical pattern with a pitch of 1.5 nm and with 4.4 subunits per turn (Fig. 7-7). The protein rods are inclined to the helix axis and extend inward. This arrangement permits a "knobs-in-holes" hydrophobic bonding between subunits. The helix of pitch 1.5 nm is the primary or one-start helix. However, in every regular helical structure we can also trace a two-start helix, a three-start helix, etc. In this instance the five-start helix is easiest to see. 

Anotiier characteristic of die inner mitochondrial membrane is the presence of projections on the inside surface, which faces the mitochondrial matrix. See Fig. 18-14. These spherical 85-kDa particles, discovered by Fernandez Moran in 1962 and attached to die membrane tiirough a "stalk", display ATP-hydrolyzing (ATPase) activity. The latter was a clue that the knobs might participate in the synthesis of ATP during oxidative phosphorylation. In fact, tiiey are now recognized as a complex of proteins called coupling factor 1 (F ) or ATP synthase. 

Diagrammatic sketch of a leucine zipper dimer. The protein monomers are held together by interaction between leucine side chains (green knobs in the upper part of the structure). The part of the protein monomers that interacts with the major groove of the DNA is shown (in red). (Adapted from C. R. Vinson et al Science 246 911, 1989.)... 

Fig. 9. Coiled-coil spirals. For the phage coat proteins and flagellin, subunits are shown enlarged next to the structures, as well as the cross sections of the coiled-coil sheets they form. The positions of the subunits in the structures are indicated in white. The core packing layers are also shown for the phage coat proteins in order to illustrate the use of knobs-into-holes and ridges-into-grooves layers.

Fig. 12. Coiled coils arising between helices that are part of different folds, (a) Soluble proteins, (b) Example of a membrane protein. Inner membrane proteins are Q-helical proteins with an up-and-down topology their helices therefore favor low crossing angles and frequently show mixtures of knobs-into-holes and ridges-into-...

Fig. 5. Schematic diagram of complementary binding sites or knob-hole interactions in fibrin polymerization. Fibrinopeptides in the central domain cover knobs that are complementary to holes that are always exposed at the ends of the protein. When the fibrinopeptides are removed by thrombin, knob-hole interactions occur, giving rise to the two-stranded protofibril made up of half-staggered molecules.

I. Kirby, E. Davison, A. J. Beavil, C. P. Soh, T. J. Wickham, P. W. Roelvink, I. Kovesdi, B. J. Sutton, and G. Santis, Mutations in the DG loop of adenovirus type 5 fiber knob protein abolish high-affinity binding to its cellular receptor CAR, J. Virol. 73 9508 (1999). 

A coiled coil is a protein bundle of 2-5 alpha helices wrapped around each other into a superhelix, also called a supercoil (Lupas, 1996a Mason and Arndt, 2004 Lupas and Gruber, 2005). In the simplest form of coiled coil, helical domains of two proteins wind around one another and bind via a distinctive knobs-into-holes pattern whereby an amino acid side chain of one helix (knob) inserts into a space surrounded by four side chains of the facing helix (hole) as first suggested by Francis Crick in 1952 (Lupas, 1996a Lupas and Gruber, 2005). 

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