Zinc finger motif for single‐stranded nucleic acids? investigations by nuclear magnetic resonance

Summers, Michael F.

doi:10.1002/jcb.240450110

Cited by 67 publications

(38 citation statements)

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“…CCHH zinc finger motif found widely in proteins that bind duplex DNA (Summers, 1991). The solution-state structure of the HIV-1 NC may be best described as a flexible polypeptide chain containing independently folded, noninteracting CCHC-type zinc finger domains.…”

Section: Discussionmentioning

confidence: 99%

“…These findings, together with sitedirected mutagenesis (Gorelick et al, 1988;Meric & Goff, 1989) and structural results (Summers et al, 1990;South et al, 1991) provide what is now overwhelming evidence for the physiological relevance of the CCHC zinc finger motif in retroviruses. CCHC zinc finger sequences have been observed recently in nucleic acid binding proteins from Xenopus (Sato & Sargent, 1991) and humans (Rajavashisth et al, 1989) and may thus provide a generic structural motif for proteins that bind single-stranded nucleic acids (Summers, 1991).…”

Section: Hiv-i Nucleocapsid Proteinmentioning

confidence: 99%

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Nucleocapsid zinc fingers detected in retroviruses: EXAFS studies of intact viruses and the solution‐state structure of the nucleocapsid protein from HIV‐1

Henderson²,

et al. 1992

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All retroviral nucleocapsid (NC) proteins contain one or two copies of an invariant 3Cys‐1His array (CCHC = C‐X2‐C‐X4‐H‐X4‐C; C = Cys, H = His, X = variable amino acid) that are essential for RNA genome packaging and infectivity and have been proposed to function as zinc‐binding domains. Although the arrays are capable of binding zinc in vitro, the physiological relevance of zinc coordination has not been firmly established. We have obtained zinc‐edge extended X‐ray absorption fine structure (EXAFS) spectra for intact retroviruses in order to determine if virus‐bound zinc, which is present in quantities nearly stoichiometric with the CCHC arrays (Bess, J.W., Jr., Powell, P.J., Issaq, H.J., Schumack, L.J., Grimes, M.K., Henderson, L.E., & Arthur, L.O., 1992, J. Virol. 66, 840–847), exists in a unique coordination environment. The viral EXAFS spectra obtained are remarkably similar to the spectrum of a model CCHC zinc finger peptide with known 3Cys‐1His zinc coordination structure. This finding, combined with other biochemical results, indicates that the majority of the viral zinc is coordinated to the NC CCHC arrays in mature retroviruses. Based on these findings, we have extended our NMR studies of the HIV‐1 NC protein and have determined its three‐dimensional solution‐state structure. The CCHC arrays of HIV‐1 NC exist as independently folded, noninteracting domains on a flexible polypeptide chain, with conservatively substituted aromatic residues forming hydrophobic patches on the zinc finger surfaces. These residues are essential for RNA genome recognition, and fluorescence measurements indicate that at least one residue (Trp37) participates directly in binding to nucleic acids in vitro. The NC is only the third HIV‐1 protein to be structurally characterized, and the combined EXAFS, structural, and nucleic acid‐binding results provide a basis for the rational design of new NC‐targeted antiviral agents and vaccines for the control of AIDS.

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Section: Discussionmentioning

confidence: 99%

Section: Hiv-i Nucleocapsid Proteinmentioning

confidence: 99%

Nucleocapsid zinc fingers detected in retroviruses: EXAFS studies of intact viruses and the solution‐state structure of the nucleocapsid protein from HIV‐1

Henderson²,

et al. 1992

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“…CCHC-type zinc finger motifs have been found in one or two copies in the retroviral nucleocapsid proteins and their Gag precursors (19) and in proteins of plant viruses and of eukaryotic cells. It has been suggested that this type of zinc finger is involved in binding of single-stranded nucleic acids (20). UMSBP belongs to a distinct group of cellular proteins that contains several (5-9) adjacent CCHC motifs, including cellular nucleic acid binding protein (CNBP) from human and mouse, which binds a G-rich single-stranded sequence of a sterol regulatory element (21); hexamer binding protein (HEXBP) from Leishmania major, which binds a G-rich singlestranded repeated sequence found in the 5Ј-untranslated region of the gene encoding GP63 (22); byr3 from Schizosacharomyces pombe (23); and CnjB from Tetrahymena thermophila (24).…”

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confidence: 99%

Universal Minicircle Sequence Binding Protein, a CCHC-type Zinc Finger Protein That Binds the Universal Minicircle Sequence of Trypanosomatids

Tzfati

Abeliovich

Avrahami

et al. 1995

Journal of Biological Chemistry

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Replication of kinetoplast DNA minicircles of trypanosomatids initiates at a conserved 12-nucleotide sequence, termed the universal minicircle sequence (UMS, 5-GGGGTTGGTGTA-3). A single-stranded nucleic acid binding protein that binds specifically to this origin-associated sequence was purified to apparent homogeneity from Crithidia fasciculata cell extracts. This UMS-binding protein (UMSBP) is a dimer of 27.4 kDa with a 13.7-kDa protomer. UMSBP binds single-stranded DNA as well as single-stranded RNA but not doublestranded or four-stranded DNA structures. Stoichiometry analysis indicates the binding of UMSBP as a protein dimer to the UMS site. The five CCHC-type zinc finger motifs of UMSBP, predicted from its cDNA sequence, are similar to the CCHC motifs found in retroviral Gag polyproteins. The remarkable conservation of this motif in a family of proteins found in eukaryotic organisms from yeast and protozoa to mammals is discussed.Kinetoplast DNA (kDNA) 1 is a unique extrachromosomal DNA network found in the single mitochondrion of parasitic flagellated protozoa of the family Trypanosomatidae. In Crithidia fasciculata, kDNA consists of about 5,000 DNA minicircles (2.5 kilobase pairs each) and about 50 DNA maxicircles (37 kilobase pairs each) interlocked topologically to form a huge DNA network (for review, see Refs. 1-3). Minicircles are heterogeneous in their nucleotide sequence but contain two short sequences, 70 -100 base pairs apart, that are conserved in all the species studied so far: the dodecamer sequence known as universal minicircle sequence (UMS), 5Ј-GGGGTTGGTGTA-3Ј, and the hexamer sequence 5Ј-ACGCCC-3Ј.On the basis of in vivo observations, Englund and co-workers (4 -8) have described the replication of kDNA minicircles as a process in which individual minicircles are detached from the central zone of the disc-shaped network, replicated, and reattached to the periphery of the disc. The network increases in size until it doubles and then divides and segregates into two daughter networks. Extensive studies of minicircle replication intermediates (9 -16) have suggested that replication begins at the UMS site with synthesis of an RNA primer and proceeds by continuous elongation of the leading light strand (L-strand). A single gap of 6 -10 nucleotides remains in the newly synthesized light strand at the UMS site (13) and is repaired only after replication of the minicircles and their reattachment to the network have been completed (8). Discontinuous synthesis of the lagging heavy strand (H-strand) starts when its origin, containing the conserved hexamer sequence, is exposed by the advancing replication fork. Highly gapped and nicked nascent H-strands are generated.We have previously reported on the recognition of UMS by a unique sequence-specific single-stranded DNA binding protein from C. fasciculata (17) and on the isolation and analysis of the UMSBP-encoding cDNA (18). The amino acid sequence of the polypeptide, predicted from the cDNA, is 116 residues long and contains five Cys-X 2 -Cys-X 4 -His-...

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“…1 A and C), distinguish glh-i from other known RNA helicases. The zinc fingers are of the CC/HC type found in the retroviral NBPs and the CNBP, the former of which has been shown to bind Zn2+, viral genomic RNA, and coding-strand DNA (30,33,34). The presence of this type of zinc finger motif further predicts that the glh-1 protein interacts with a single-stranded nucleic acid, possibly an RNA or population of RNAs.…”

Section: Resultsmentioning

confidence: 99%

glh-1, a germ-line putative RNA helicase from Caenorhabditis, has four zinc fingers.

Roussell

Bennett

1993

Proc. Natl. Acad. Sci. U.S.A.

118

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We have cloned a family of putative RNA helicases from the free-living nematode Caenorhabditis elegans. One of these, a cDNA that we call glh-1, most dosely matches in sequence and expression the previously described germ-line helicases PL10 from mouse and vasa from Drosophila. The amino terminus of the predicted protein of glh-) contains a set of glycine-rich repeats similar in location and sequence to those in the predicted vasa protein. However, unlike all other putative RNA helicases, glh-l also contains four retroviral-type zinc fingers. The RNA expression pattern ofthis Caenorhabditis helicase correlates with the presence of germ-line tissue in the parasitic nematodeAscaris lumbricoides var. suum and with the presence of germ cells in wild type and several germ-line mutants of Caenorhabditis. In the germ-line mutants glp-4 and gip-1, additional larger species of glh-l RNA exist, which correspond to different adenylylated forms of the glh-l transcript; these may be specified by motifs in the 3' untranslated region of glh-) that are similar to adenylylation control elements and nos response elements.

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Zinc finger motif for single‐stranded nucleic acids? investigations by nuclear magnetic resonance

Cited by 67 publications

References 38 publications

Nucleocapsid zinc fingers detected in retroviruses: EXAFS studies of intact viruses and the solution‐state structure of the nucleocapsid protein from HIV‐1

Nucleocapsid zinc fingers detected in retroviruses: EXAFS studies of intact viruses and the solution‐state structure of the nucleocapsid protein from HIV‐1

Universal Minicircle Sequence Binding Protein, a CCHC-type Zinc Finger Protein That Binds the Universal Minicircle Sequence of Trypanosomatids

glh-1, a germ-line putative RNA helicase from Caenorhabditis, has four zinc fingers.

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