Cyclin fold

TFIIB is arranged in two domains, both of which have the cyclin fold described in Chapter 6. Both domains bind to the TBP-TATA box complex at the C-terminal stirrup and helix of TBP. The phosphate and sugar moities of DNA form extensive non-sequence-specific contacts with TFIIB both upstream and downstream of the middle of the TATA box. 

Figure 13.30 Ribbon diagram of the structure of Src tyrosine kinase. The structure is divided in three units starting from the N-terminus an SH3 domain (green), an SH2 domain (blue), and a tyrosine kinase (orange) that is divided into two domains and has the same fold as the cyclin dependent kinase described in Chapter 6 (see Figure 6.16a). The linker region (red) between SH2 and the kinase is bound to SH3 in a polyproline helical conformation. A tyrosine residue in the carboxy tail of the kinase is phosphorylated and bound to SH2 in its phosphotyrosine-binding site. A disordered part of the activation segment in the kinase is dashed. (Adapted from W. Xu et al.. Nature 385 595-602, 1997.)...

FIGURE 12-44 Regulation of CDK by phosphorylation and proteolysis. (a) The cyclin-dependent protein kinase activated at the time of mitosis (the M phase CDK) has a "T loop" that can fold into the substrate-binding site. When Thr150 in the T loop is phosphorylated, the loop moves out of the substrate-binding site, activating the CDK... 

Right Structural scheme of the cyclin-box motif of cyclin A to which the p27kif-t binds. The peptidebinding groove of cyclin A. in purple, is filled by the green balls of the p27 - protein. The cyclin box is a rather common, stable structural fold, which comprises a bundle of five tandemly repeated a-helices. On the surface of the cyclin box are clusters of conserved residues, which, in the case of the cyclin A-Cdkl pair, have been shown to be part of the interaction surface of the cyclin with the cognate kinase. 

CDK2 has a folding pattern similar to that of the other structurally characterized Ser-specific protein kinases. Comparison of the inactive form of CDK2 (Fig. 13.8) with the cyclin A-bound form and with the active form of protein kinase A shows that there are two main causes of the inactivity of CDK2 without bound cyclin. Firstly, in the inactive form, the binding site for the protein substrate is blocked by a loop known as the T-... 

On the other hand, it has been suggested, based on immunopre-cipitation reactions, that CCT might interact with a broad range (accounting for 9-15%) of newly synthesized eukaryotic proteins (Feldman and Frydman, 2000 McCallum et al., 2000 Thulasiraman et al., 1999). There is also evidence that some proteins other than actins and tubulins fold via interaction with CCT. These include G -transducin (Farr etal, 1997), cyclinE (Won etal., 1998), and the von Hippel-Landau tumor suppressor protein VHL (Feldman et al., 1999). Moreover, translation in vitro of myosin heavy and light chains has identified an intermediate in the biogenesis of the heavy meromyosin subunit (HMM) of skeletal muscle myosin that contains all three myosin subunits and CCT, from which partially folded HMM can be released in an ATP-dependent reaction. Other as yet unknown cytosolic protein(s) are also apparently required for the completion of the myosin folding reaction (Srikakulam and Winkelmann, 1999). 

---