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Short Loops (short + loop)

Distribution by Scientific Domains

Chemistry	100%

Selected Abstracts

Synthesis and NMR solution structure of an ,-helical hairpin stapled with two disulfide bridges

PROTEIN SCIENCE, Issue 5 2000
Philippe Barthe
Abstract Helical coiled-coils and bundles are some of the most common structural motifs found in proteins. Design and synthesis of ,-helical motifs may provide interesting scaffolds that can be useful as host structures to display functional sites, thus allowing the engineering of novel functional miniproteins. We have synthesized a 38-amino acid peptide, ,2p8, encompassing the ,-helical hairpin present in the structure of p8MTCP1, as an ,-helical scaffold particularly promising for its stability and permissiveness of sequence mutations. The three-dimensional structure of this peptide has been solved using homonuclear two-dimensional NMR techniques at 600 MHz. After sequence specific assignment, a total of 285 distance and 29 dihedral restraints were collected. The solution structure of ,2p8 is presented as a set of 30 DIANA structures, further refined by restrained molecular dynamics, using simulated annealing protocol with the AMBER force field. The RMSD values for the backbone and all heavy atoms are 0.65 ± 0.25 and 1.51 ± 0.21 Å, respectively. Excised from its protein context, the ,-hairpin keeps its native structure: an ,-helical coiled-coil, similar to that found in superhelical structures, with two helices spanning residues 4-16 and 25,36, and linked by a short loop. This motif is stabilized by two interhelical disulfide bridges and several hydrophobic interactions at the helix interface, leaving most of its solvent-exposed surface available for mutation. This ,-helical hairpin, easily amenable to synthetic chemistry and biological expression system, may represent a stable and versatile scaffold to display new functional sites and peptide libraries. [source]

Closed loop folding units from structural alignments: Experimental foldons revisited

JOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 15 2010
Sree V. Chintapalli
Abstract Nonoverlapping closed loops of around 25,35 amino acids formed via nonlocal interactions at the loop ends have been proposed as an important unit of protein structure. This hypothesis is significant as such short loops can fold quickly and so would not be bound by the Leventhal paradox, giving insight into the possible nature of the funnel in protein folding. Previously, these closed loops have been identified either by sequence analysis (conservation and autocorrelation) or studies of the geometry of individual proteins. Given the potential significance of the closed loop hypothesis, we have explored a new strategy for determining closed loops from the insertions identified by the structural alignment of proteins sharing the same overall fold. We determined the locations of the closed loops in 37 pairs of proteins and obtained excellent agreement with previously published closed loops. The relevance of NMR structures to closed loop determination is briefly discussed. For cytochrome c, cytochrome b562 and triosephophate isomerase, independent folding units have been determined on the basis of hydrogen exchange experiments and misincorporation proton-alkyl exchange experiments. The correspondence between these experimentally derived foldons and the theoretically derived closed loops indicates that the closed loop hypothesis may provide a useful framework for analyzing such experimental data. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010 [source]

Long membrane helices and short loops predicted less accurately

PROTEIN SCIENCE, Issue 12 2002
Chien Peter Chen
3D, three-dimensional; DSSP, program assigning secondary structure (Kabsch and Sander 1983); HMM, hidden Markov model; PDB, Protein Data Bank of experimentally determined 3D structures of proteins (Bernstein et al. 1977; Berman et al. 2000); SWISS-PROT, database of protein sequences (Bairoch and Apweiler 2000); TM, transmembrane; TMH, transmembrane helix Abstract Low-resolution experiments suggest that most membrane helices span over 17,25 residues and that most loops between two helices are longer than 15 residues. Both constraints have been used explicitly in the development of prediction methods. Here, we compared the largest possible sequence,unique data sets from high- and low-resolution experiments. For the high-resolution data, we found that only half of the helices fall into the expected length interval and that half of the loops were shorter than 10 residues. We compared the accuracy of detecting short loops and long helices for 28 advanced and simple prediction methods: All methods predicted short loops less accurately than longer ones. In particular, loops shorter than 7 residues appeared to be very difficult to detect by current methods. Similarly, all methods tended to be more accurate for longer than for shorter helices. However, helices with more than 32 residues were predicted less accurately than all other helices. Our findings may suggest particular strategies for improving predictions of membrane helices. [source]