Crystal structures of an HIV-1 integrase aptamer: Formation of a water-mediated A•G•G•G•G pentad in an interlocked G-quadruplex

Structural Basis for Parallel G-Quadruplex Recognition by an Ankyrin Protein

“…The structure of the 2E4–93del-T12 complex was determined at 2.0 Å in the P 2 1 2 1 2 space group (see Table S1 for structural statistics), with one protein molecule and a monomer of 93del-T12 per asymmetric unit (Figure ). 93del-T12 forms an interlocked dimeric parallel G4 similar to what was previously observed . The two exposed G-tetrads of the dimeric G4 are bound by two 2E4 molecules, one to each 3′-end terminal G-tetrad (Figure ).…”

“…93del-T12 forms an interlocked dimeric parallel G4 similar to what was previously observed. 57 The two exposed G-tetrads of the dimeric G4 are bound by two 2E4 molecules, one to each 3′end terminal G-tetrad (Figure 2). Overall, a bundle of helices and loops of the protein together form an anchor surface that can dock onto the G-tetrad (Figures 2D and 3A−C).…”

“…Next, we investigated by gel electrophoresis the binding of 2E4 with different parallel G4s, including various DNA G4s and an RNA G4 formed by a TERRA sequence (Table ). Despite variation in the 3′-end sequence ( c-MYC vs c-MYC-7T) , the stoichiometry (monomeric T95-2T vs dimeric T95/93del-T12 ), , or the type of nucleic acids (DNA vs RNA), 2E4 could bind to all investigated parallel G4-forming sequences (Figure S4). Additionally, the interaction between 2E4 and some G4 structures ( T95 and 93del-T12 ) was confirmed by 1 H NMR titration experiments (Figure S5), which showed additional NMR imino proton peaks upon 2E4 addition.…”

“…2E4 was crystallized in its free form and co-crystallized with a parallel G4 ( 93del-T12 ) (Figure S6). The structure of 2E4 was determined at 2.0 Å resolution in the P 12 1 1 space group.…”

Comprehensive analysis of intramolecular G-quadruplex structures: furthering the understanding of their formalism

“…Two structures (2IDN ( 61 ) and 3QLP ( 62 )) have a 5′–5′ inversion of polarity site, meaning that the nucleic acid chain starts with a 3′ extremity and, after a number of nts (here three), the chain is reversed with a 5′–5′ link to continue normally until the end. Seven structures are interlaced dimers (1JJP ( 63 ), 1Y8D ( 64 ), 7X7G ( 65 ), 7XDH ( 65 ), 7XH9 ( 65 ), 7XHD ( 65 ) and 7XIE ( 65 )), meaning that, in each monomer, the first tetrad is made of three guanosines from this monomer plus one guanosine from the other monomer, to complete the tetrad. Moreover, there are two monomers with an additional guanosine that is not part of the nucleotide chain, but which inserts in the first tetrad (7MSV ( 66 )) or the last tetrad (6K3X ( 67 )) to complete it.…”