Home About us Contact
|
Home About us Contact | ||
|
|
||
Helix Interactions (helix + interaction)
Selected AbstractsUniformly Nucleobase-Functionalized ,-Peptide Helices: Watson,Crick Pairing or Nonspecific AggregationEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 33 2007Angelina Weiß Abstract The organization and architecture of helices is fundamental in folding of protein tertiary structures. Therefore, stable ,-peptide helices are used as models for the selective organization of secondary structures. Nucleobases are already established as recognition elements to organize two ,-peptide helices in antiparallel orientation. The investigation of ,-peptide helices uniformly functionalized with one type of nucleobases provided further insight in the recognition mode and requirements for specific interaction within the linear and very rigid helical backbone topology. Specific helix interaction based on base pair recognition is predominant as soon as Watson,Crick pairing is allowed. If the hydrogen bonding donor/acceptor pattern prohibits the Watson,Crick geometry, a quite stable nonspecific interaction was found based on aromatic interactions or on a nonspecific hydrogen bonding network. The latter aggregation was also confirmed with tyrosine side chains.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Inactivation of colicin Y by intramembrane helix,helix interaction with its immunity proteinFEBS JOURNAL, Issue 21 2008David, majs The construction of hybrids between colicins U and Y and the mutagenesis of the colicin Y gene (cya) have revealed amino acid residues important for interactions between colicin Y and its cognate immunity protein (Cyi). Four such residues (I578, T582, Y586 and V590) were found in helices 8 and 9 of the colicin Y pore-forming domain. To verify the importance of these residues, the corresponding amino acids in the colicin B protein were mutated to the residues present in colicin Y. An Escherichia coli strain with cloned colicin Y immunity gene (cyi) inactivated this mutant, but not the wild-type colicin B. In addition, interacting amino acid pairs in Cya and Cyi were identified using a set of Cyi point mutant strains. These data are consistent with antiparallel helix,helix interactions between Cyi helix T3 and Cya helix 8 of the pore-forming domain as a molecular mechanism of colicin Y inactivation by its immunity protein. [source] Identification of regions of leukotriene C4 synthase which direct the enzyme to its nuclear envelope localizationJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2006Jesper Svartz Abstract Leukotrienes (LTs) are fatty acid derivatives formed by oxygenation of arachidonic acid via the 5-lipoxygenase (5-LO) pathway. Upon activation of inflammatory cells 5-LO is translocated to the nuclear envelope (NE) where it converts arachidonic acid to the unstable epoxide LTA4. LTA4 is further converted to LTC4 by conjugation with glutathione, a reaction catalyzed by the integral membrane protein LTC4 synthase (LTC4S), which is localized on the NE and endoplasmic reticulum (ER). We now report the mapping of regions of LTC4S that are important for its subcellular localization. Multiple constructs encoding fusion proteins of green fluorescent protein (GFP) as the N-terminal part and various truncated variants of human LTC4S as C-terminal part were prepared and transfected into HEK 293/T or COS-7 cells. Constructs encoding hydrophobic region 1 of LTC4S (amino acids 6,27) did not give distinct membrane localized fluorescence. In contrast hydrophobic region 2 (amino acids 60,89) gave a localization pattern similar to that of full length LTC4S. Hydrophobic region 3 (amino acids 114,135) directed GFP to a localization indistinguishable from that of full length LTC4S. A minimal directing sequence, amino acids 117,132, was identified by further truncation. The involvement of the hydrophobic regions in the homo-oligomerization of LTC4S was investigated using bioluminescence resonance energy transfer (BRET) analysis in living cells. BRET data showed that hydrophobic regions 1 and 3 each allowed oligomerization to occur. These regions most likely form transmembrane helices, suggesting that homo-oligomerization of LTC4S is due to helix,helix interactions in the membrane. J. Cell. Biochem. 98: 1517,1527, 2006. © 2006 Wiley-Liss, Inc. [source] Transmembrane signal transduction of the ,IIb,3 integrinPROTEIN SCIENCE, Issue 7 2002Kay E. Gottschalk Abstract Integrins are composed of noncovalently bound dimers of an ,- and a ,-subunit. They play an important role in cell-matrix adhesion and signal transduction through the cell membrane. Signal transduction can be initiated by the binding of intracellular proteins to the integrin. Binding leads to a major conformational change. The change is passed on to the extracellular domain through the membrane. The affinity of the extracellular domain to certain ligands increases; thus at least two states exist, a low-affinity and a high-affinity state. The conformations and conformational changes of the transmembrane (TM) domain are the focus of our interest. We show by a global search of helix,helix interactions that the TM section of the family of integrins are capable of adopting a structure similar to the structure of the homodimeric TM protein Glycophorin A. For the ,IIb,3 integrin, this structural motif represents the high-affinity state. A second conformation of the TM domain of ,IIb,3 is identified as the low-affinity state by known mutational and nuclear magnetic resonance (NMR) studies. A transition between these two states was determined by molecular dynamics (MD) calculations. On the basis of these calculations, we propose a three-state mechanism. [source] End-to-end and end-to-middle interhelical interactions: new classes of interacting helix pairs in protein structuresACTA CRYSTALLOGRAPHICA SECTION D, Issue 10 2009Tarini Shankar Ghosh Helix,helix interactions are important for the structure, stability and function of ,-helical proteins. Helices that either cross in the middle or show extensive contacts between each other, such as coiled coils, have been investigated in previous studies. Interactions between two helices can also occur only at the terminal regions or between the terminal region of one helix and the middle region of another helix. Examples of such helix pairs are found in aquaporin, H+/Cl, transporter and Bcl-2 proteins. The frequency of the occurrence of such `end-to-end' (EE) and `end-to-middle' (EM) helix pairs in protein structures is not known. Questions regarding the residue preferences in the interface and the mode of interhelical interactions in such helix pairs also remain unanswered. In this study, high-resolution structures of all-, proteins from the PDB have been systematically analyzed and the helix pairs that interact only in EE or EM fashion have been extracted. EE and EM helix pairs have been categorized into five classes (N,N, N,C, C,C, N,MID and C,MID) depending on the region of interaction. Nearly 13% of 5725 helix pairs belonged to one of the five classes. Analysis of single-residue propensities indicated that hydrophobic and polar residues prefer to occur in the C-terminal and N-terminal regions, respectively. Hydrophobic C-terminal interacting residues and polar N-terminal interacting residues are also highly conserved. A strong correlation exists between some of the residue properties (surface area/volume and length of side chains) and their preferences for occurring in the interface of EE and EM helix pairs. In contrast to interacting non-EE/EM helix pairs, helices in EE and EM pairs are farther apart. In these helix pairs, residues with large surface area/volume and longer side chains are preferred in the interfacial region. [source] Ligand-induced activation of the insulin receptor: a multi-step process involving structural changes in both the ligand and the receptorBIOESSAYS, Issue 4 2009Colin W. Ward Abstract Current models of insulin binding to the insulin receptor (IR) propose (i) that there are two binding sites on the surface of insulin which engage with two binding sites on the receptor and (ii) that ligand binding involves structural changes in both the ligand and the receptor. Many of the features of insulin binding to its receptor, namely B-chain helix interactions with the leucine-rich repeat domain and A-chain residue interactions with peptide loops from another part of the receptor, are also seen in models of relaxin and insulin-like peptide 3 binding to their receptors. We show that these principles can likely be extended to the group of mimetic peptides described by Schäffer and coworkers, which are reported to have no sequence identity with insulin. This review summarizes our current understanding of ligand-induced activation of the IR and highlights the key issues that remain to be addressed. [source] | |||||||||||||