A short survey on protein blocks

Abstract

Protein structures are classically described in terms of secondary structures. Even if the regular secondary structures have relevant physical meaning, their recognition from atomic coordinates has some important limitations such as uncertainties in the assignment of boundaries of helical and β-strand regions. Further, on an average about 50% of all residues are assigned to an irregular state, i.e., the coil. Thus different research teams have focused on abstracting conformation of protein backbone in the localized short stretches. Using different geometric measures, local stretches in protein structures are clustered in a chosen number of states. A prototype representative of the local structures in each cluster is generally defined. These libraries of local structures prototypes are named as "structural alphabets". We have developed a structural alphabet, named Protein Blocks, not only to approximate the protein structure, but also to predict them from sequence. Since its development, we and other teams have explored numerous new research fields using this structural alphabet. We review here some of the most interesting applications.

Fig. 1

Principle of encoding of protein structures using a “structural alphabet”. The N-terminal extremity of chain B of Aspergillus niger acid phosphatase (Kostrewa et al. 1999) (a) is encoded in terms of a structural alphabet (b). Each residue is approximated by a specific prototype—here a protein block (PB). Hence, the crude description as a coil region (determined by any secondary structure assignment method) is replaced by a more precise series of PBs dcbdfkl

Fig. 2

The protein blocks. PBs from a to p are shown using PyMol software (DeLano 2002).. For each PB, the N -ap extremity is shown on the left and the C-cap on the right. Each prototype is five residues in length and corresponds to eight dihedral angles (φ,ψ). The PBs m and d are mainly associated to the central region of α-helix and the central region of β-strand, respectively (de Brevern ; de Brevern et al. 2000)

Fig. 3

An example of difficult superimposition of three-dimension (3D) protein structures using PBs. The 3D structure of the Aspergillus niger acid phosphatase (Kostrewa et al. 1999) chain B has been superimposed on the 3D structure of Escherichia coli periplasmic glucose-1-phosphatase chain A (Lee et al. 2003). a, b Superimposition using a previous approach (Tyagi et al. 2006b), c, d superimposition with the novel approach. Using regions of high similarity as seeds (blue, gold and pink), as shown in e, the root mean square deviation is 17 Å lower than the value previously computed

Fig. 4

An example of a hard case of superimposition of 3D protein structures using PBs. The 3D superimposition shown in Fig. 3 is presented here as the PB alignment. Repetitive PBs and direct N-cap and C-cap are shown in color