Protein crossover connections

Besides hairpin turns and broader U-tums, a protein chain may turn out and fold back to reenter a P sheet from the opposite side. Such crossover connections, which are necessarily quite long, often contain helices. Like turns, crossover connections have a handedness and are nearly always right-handed (Fig. 2-25).117/219 Most proteins also contain poorly organized loops on their surfaces. Despite their random appearance, these loops may be critical for the functioning of a protein.220 In spite of the complexity of the folding patterns, peptide chains are rarely found to be knotted.221... 

Figure 2-25 Right- and left-handed crossover connections in proteins. These connections are nearly always right-handed. The broad arrows represent (S strands. The crossover often contains a helix. Units of two adjacent P strands ( 3a 3 units) with an a helix between are found frequently in globular proteins.

The TRAF2-TRADD interaction is mediated by the TRAF domain of TRAF2 and the N-terminal domain of TRADD (TRADD-N). The TRADD-N domain has so far only been found in mammalian TRADD proteins. It folds into an a-/3 sandwich with a four-stranded /3-sheet and six a-helices, each forming one layer of the structure (Park et al, 2000 Tsao et al, 2000) (Fig. 9A). The /3-sheet is entirely anti-parallel and slightly twisted with a strand order of /32, /33, /31, and /34. There are two helices each in the /31-/32 and /3S-/34 crossover connections while the /32-/3S connection is hairpin-like. The remaining two helices (E and F) are near the carboxy-terminus of the domain the loop in between (EF loop) pardy covers one end of the exposed face of the /3-sheet. 

Proteins built up entirely from a-helices include the globin and hanerythrin families and bacterioihodopsin. These are transport proteins and membrane-bound proteins. All-P proteins invariably consist of a sandwich of two layers, each a sheet held together by a hydrophobic core formed by one side from each sheet. Often the sheet is rounded to form a P-barrel. The P interactions in these proteins are usually antiparallel because there are no helices available to form the necessary crossover connections required for parallel P-sheets. The novel family of proteins with an all-parallel P-helix (Jumak et al, 1994 Yoder et al, 1993) is a remarkable exception. Proteins with distinct regions of all-a or all-P structures are called a + P proteins. The most complex class is the o/p proteins. In these, segments of a-helix and P-sheet follow one another, and consequently each of the two classes of secondary structure is intimately involved in stabilization of the other. For this reason, the P-structures are often parallel, since the presence of helices provides the necessary crossover connections. The -class of proteins is an ill-defined catchall (Chou, 1995). It includes a number of large peptides with no globular structure. 

PaP motif A commonly encountered motif found in protein structures. It consists of two P strands connected by an a helix. The crossover that this provides is right-handed. 

The obtained MD simulation results together with the confirmation of this dynamic crossover in protein hydration water suggest that it may be connected to the first stage of the unfolding process of the protein. The protein backbone RMSD calculated from the trajectories shows a sudden increase between 330 and 340K (Fig. 24), signaling the beginning of the denaturation process. 

---