Structural Basis for the Identification of an i-Motif Tetraplex Core with a Parallel-Duplex Junction as a Structural Motif in CCG Triplet Repeats

2014 ◽  
Vol 126 (40) ◽  
pp. 10858-10862 ◽  
Author(s):  
Yi-Wen Chen ◽  
Cyong-Ru Jhan ◽  
Stephen Neidle ◽  
Ming-Hon Hou
Keyword(s):  
Structural Motif ◽  
Structural Basis ◽  
Triplet Repeats

Structural basis of the binding of Actinomycin D to CGG triplet repeats

2014 ◽  
Author(s):  
Yu-Sheng Lo ◽  
Wen-Hsuan Tseng ◽  
Chien-Ying Chuang ◽  
Ming-Hon Hou
Keyword(s):  
Actinomycin D ◽  
Structural Basis ◽  
Triplet Repeats

scholarly journals Structural basis for acyl chain control over glycosphingolipid sorting and vesicular trafficking

2021 ◽  
Author(s):  
Stefanie S. Schmieder ◽  
Raju Tatituri ◽  
Michael Anderson ◽  
Kate Kelly ◽  
Wayne I. Lencer
Keyword(s):  
Acyl Chain ◽  
Vesicular Trafficking ◽  
Structural Motif ◽  
Structural Basis ◽  
Membrane Organization ◽  
Endosomal Sorting ◽  
Lysosomal Sorting ◽  
Acyl Chains ◽  
Complex Sphingolipids ◽  
Endocytic Pathways

AbstractThe complex sphingolipids exhibit a diversity of ceramide acyl chain structures that influence their trafficking and intracellular distributions, but how the cell discerns among the different ceramides to affect such sorting remains unknown. To address mechanism, we synthesized a library of GM1 glycosphingolipids with naturally varied acyl chains and quantitatively assessed their sorting among different endocytic pathways. We found that a stretch of at least 14 saturated carbons extending from C1 at the water-bilayer interface dictated lysosomal sorting by exclusion from endosome sorting tubules. Sorting to the lysosome by the C14*-motif was cholesterol dependent. Perturbations of the C14*-motif by unsaturation enabled GM1 entry into endosomal sorting tubules of the recycling and retrograde pathways independently of cholesterol. Unsaturation occurring beyond the C14*-motif in very long acyl chains rescued lysosomal sorting. These results define a structural motif underlying membrane organization of sphingolipids and implicate cholesterol-sphingolipid nanodomain formation in sorting mechanisms.

scholarly journals Structural basis of transcriptional stalling and bypass of abasic DNA lesion by RNA polymerase II

2018 ◽  
Vol 115 (11) ◽  
pp. E2538-E2545 ◽  
Author(s):  
Wei Wang ◽  
Celine Walmacq ◽  
Jenny Chong ◽  
Mikhail Kashlev ◽  
Dong Wang
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Dna Lesions ◽  
Structural Motif ◽  
Structural Basis ◽  
Dependent Manner ◽  
Abasic Site ◽  
Structural Explanation ◽  
Pol Ii ◽  
Abasic Sites

Abasic sites are among the most abundant DNA lesions and interfere with DNA replication and transcription, but the mechanism of their action on transcription remains unknown. Here we applied a combined structural and biochemical approach for a comprehensive investigation of how RNA polymerase II (Pol II) processes an abasic site, leading to slow bypass of lesion. Encounter of Pol II with an abasic site involves two consecutive slow steps: insertion of adenine opposite a noninstructive abasic site (the A-rule), followed by extension of the 3′-rAMP with the next cognate nucleotide. Further studies provided structural insights into the A-rule: ATP is slowly incorporated into RNA in the absence of template guidance. Our structure revealed that ATP is bound to the Pol II active site, whereas the abasic site is located at an intermediate state above the Bridge Helix, a conserved structural motif that is cirtical for Pol II activity. The next extension step occurs in a template-dependent manner where a cognate substrate is incorporated, despite at a much slower rate compared with nondamaged template. During the extension step, neither the cognate substrate nor the template base is located at the canonical position, providing a structural explanation as to why this step is as slow as the insertion step. Taken together, our studies provide a comprehensive understanding of Pol II stalling and bypass of the abasic site in the DNA template.

scholarly journals The structural basis of actinomycin D–binding induces nucleotide flipping out, a sharp bend and a left-handed twist in CGG triplet repeats

2013 ◽  
Vol 41 (7) ◽  
pp. 4284-4294 ◽  
Author(s):  
Yu-Sheng Lo ◽  
Wen-Hsuan Tseng ◽  
Chien-Ying Chuang ◽  
Ming-Hon Hou
Keyword(s):  
Actinomycin D ◽  
Structural Basis ◽  
Triplet Repeats ◽  
Sharp Bend ◽  
Left Handed

Evidence that a calmodulin-like calcium-binding domain of the FSH β-subunit is involved in FSH-induced calcium uptake by Sertoli cells

1994 ◽  
Vol 13 (2) ◽  
pp. 149-155 ◽  
Author(s):  
P Grasso ◽  
L E Reichert
Keyword(s):  
Sertoli Cells ◽  
Calcium Binding ◽  
Synthetic Peptide ◽  
Calcium Uptake ◽  
Model Systems ◽  
Structural Motif ◽  
Structural Basis ◽  
Β Subunit ◽  
Amino Terminal ◽  
Binding Residue

ABSTRACT We have previously shown that a synthetic peptide amide corresponding to residues 1–15 of the human FSH β-subunit (hFSH-β-(1–15)) possesses structural characteristics and calcium-binding properties similar to the calcium-binding loops of calmodulin (CaM). The calcium-binding property of hFSH-β-(1–15) correlated well with its ability to stimulate uptake of calcium (as45 Ca2+) by cultured rat Sertoli cells and proteoliposomes enriched with bovine calf testis FSH receptors. A sequence found in the calcium-binding loops of CaM and a number of other calcium-binding proteins can be represented by the motif +−+−+−+−+−−+, where + represents a calcium-binding residue and − represents a non-binding residue. A sequence containing a similar motif appears in hFSHβ-(1–15) between residues 4 and 15: +−++−+−−−+−+. Using a synthetic peptide strategy, we undertook to determine whether the first three residues of hFSH-β-(1–15) were required to induce uptake of calcium by cultured rat Sertoli cells and FSH receptor-enriched proteoliposomes, and to assess whether rearrangement of the putative calcium-binding ligands (+) of hFSH-β-(1–15) to correspond to their linear sequence in CaM would enhance the ability of hFSH-β-(1–15) to induce calcium uptake in these two model systems. Our results indicate that (1) the amino terminal tripeptide of hFSH-β-(1–15), NSC, is not required for its effects on calcium influx and (2), although the putative calcium-binding loop of hFSH-β-(1–15) does not strictly adhere to the structural motif present in the calcium-binding loops of CaM, this does not adversely affect the potency of hFSH-β-(1–15) in the systems studied. In addition to providing a structural basis for understanding the affinity of hFSH-β-(1–15) for calcium, these studies suggest that the effects of FSH on calcium flux in Sertoli cells may involve a CaM-like region of its β-subunit.

scholarly journals Structural Basis for Antigen Recognition by Methylated Lysine Specific Antibodies

2020 ◽  
pp. jbc.RA120.015996
Author(s):  
Misaki Ishii ◽  
Makoto Nakakido ◽  
Jose M.M. Caaveiro ◽  
Daisuke Kuroda ◽  
CJ Okumura ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
De Novo ◽  
Cross Reactivity ◽  
Antigen Recognition ◽  
Structural Motif ◽  
Structural Basis ◽  
Target Antigen ◽  
Specific Antibodies ◽  
Data Capturing ◽  
Methylated Lysine

Proteins are modulated by a variety of posttranslational modifications including methylation. Despite its importance, the majority of protein methylation modifications discovered by mass spectrometric analyses are functionally uncharacterized, partly due to the difficulty in obtaining reliable methylsite-specific antibodies. To elucidate how functional methylsite-specific antibodies recognize the antigens and lead to development of novel method to create such antibodies, we use an immunized library paired with phage display to create rabbit monoclonal antibodies recognizing trimethylated Lys260 of MAP3K2 as a representative substrate. We isolated several methylsite-specific antibodies which contained unique complementarity determining region sequence.  We characterized the mode of antigen recognition by each of these antibodies using structural and biophysical analyses, revealing the molecular details, such as  binding affinity toward methylated / unmethylated antigens and s structural motif that is responsible for recognition of methylated lysine residue, by which each antibody recognized the target antigen. In addition, the comparison with the results of western blotting analysis suggests a critical antigen recognition mode to generate cross-reactivity to protein and peptide antigen of the antibodies.  Computational simulations effectively recapitulated our biophysical data, capturing the antibodies of differing affinity and specificity. Our exhaustive characterization provides molecular architectures of functional methylsite-specific antibodies and thus should contribute to the development of a general method to generate functional methylsite-specific antibodies by de novo design.

scholarly journals Structural Basis of Ist1 Function and Ist1–Did2 Interaction in the Multivesicular Body Pathway and Cytokinesis

2009 ◽  
Vol 20 (15) ◽  
pp. 3514-3524 ◽  
Author(s):  
Junyu Xiao ◽  
Xiao-Wei Chen ◽  
Brian A. Davies ◽  
Alan R. Saltiel ◽  
David J. Katzmann ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Mechanism Of Action ◽  
Intramolecular Interaction ◽  
Multivesicular Body ◽  
Structural Motif ◽  
Structural Basis ◽  
Membrane Deformation ◽  
Aaa Atpase ◽  
Cellular Processes ◽  
Escrt Machinery

The ESCRT machinery functions in several important eukaryotic cellular processes. The AAA-ATPase Vps4 catalyzes disassembly of the ESCRT-III complex and may regulate membrane deformation and vesicle scission as well. Ist1 was proposed to be a regulator of Vps4, but its mechanism of action was unclear. The crystal structure of the N-terminal domain of Ist1 (Ist1NTD) reveals an ESCRT-III subunit-like fold, implicating Ist1 as a divergent ESCRT-III family member. Ist1NTD specifically binds to the ESCRT-III subunit Did2, and cocrystallization of Ist1NTD with a Did2 fragment shows that Ist1 interacts with the Did2 C-terminal MIM1 (MIT-interacting motif 1) via a novel MIM-binding structural motif. This arrangement indicates a mechanism for intermolecular ESCRT-III subunit association and may also suggest one form of ESCRT-III subunit autoinhibition via intramolecular interaction.

scholarly journals The parallel-stranded d(CGA) duplex is a highly predictable structural motif with two conformationally distinct strands

2021 ◽  
Author(s):  
Emily M. Luteran ◽  
Paul J. Paukstelis
Keyword(s):  
Crystal Structures ◽  
Base Pair ◽  
Structural Parameters ◽  
Structural Diversity ◽  
Structural Motif ◽  
Biological Functions ◽  
Triplet Repeats ◽  
Highly Uniform ◽  
Distinct Role

ABSTRACTDNA can adopt non-canonical structures that have important biological functions while also providing structural diversity for nanotechnology applications. Here, we describe the crystal structures of two oligonucleotides composed of d(CGA) triplet repeats in the parallel-stranded duplex form. The structure determination of four unique d(CGA)-based parallel-stranded duplexes across two crystal structures has allowed us to characterize and establish structural parameters of d(CGA) triplets in the parallel-stranded duplex form. Our results show that d(CGA) units are highly uniform, but that each strand in the duplex is structurally unique and has a distinct role in accommodating structural asymmetries induced by the C-CH+ base pair.

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