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Zinc Finger Proteins: From Atomic Contact to Cellular Function


Edited By:

Shiro Iuchi
Harvard University

Natalie Kuldell
MIT

ISBN: 978-0-306-48229-8
Published: 2005-01-15

This book may be purchased as an eBook (pdf) for $99, or individual chapters (pdf) may be purchased from the list below for $19.





Chapters available from this book


ABBREVIATIONS

Shiro Iuchi

Abbreviations for the book Zinc Finger Proteins: from Atomic Contact to Cellular Function

Role of GATA Factors in Development

Marc Haenlin and Lucas Waltzer

Members of the GATA transcription factor family are found throughout eukaryotes, including plants, fungi, invertebrates and vertebrates. In this review, we discuss some of the roles of GATA factors during vertebrate and invertebrate development. We place particular emphasis on their function in...

MutM: Single C2C2 Zinc Finger-DNA Interaction

Ryoji Masui, Noriko Nakagawa and Seiki Kuramitsu

The prokaryotic MutM protein is a trifunctional DNA base excision repair enzyme that removes a wide range of oxidatively damaged bases, especially 8-oxoguanine, (Nglycosylase activity) and cleaves both the 3’- and 5’- phosphodiester bonds of the resulting apurinic/apyrimidinic site (AP lyase ac...

Tandem CCCH Zinc Finger Proteins in mRNA Binding

Perry J. Blackshear, Ruth S. Phillips and Wi S. Lai

A small family of mammalian zinc finger proteins containing an unusual putative tandem zinc finger motif was identified approximately 13 years ago. The tandem zinc finger domain was characterized by two hypothetical fingers with identical Cx8Cx5Cx3H spacing, with exactly 18 amino acids between ...

Basonuclin: A Zinc Finger Protein of Epithelial Cells and Reproductive Germ Cells

Howard Green and Hung Tseng

Basonuclin is a C2H2 zinc finger protein first discovered in the keratinocytes of stratified squamous epithelia and in certain keratinocytes of the hair follicles. It was later detected in the reproductive germ cells of the testis and ovary and in the cells of the ocular lens epithelium. The onl...

KRAB Zinc Finger Proteins: A Family of Repressors Mediating Heterochromatin- Associated Gene Silencing

Shiro Iuchi

Kruppel-associate box (KRAB) domain, present at the N terminus of mammalian C2H2 zinc finger proteins, binds KAP-1 (also named TIF1beta or KRIP-1) that binds HP1alpha and SETDB1 (H3-K9 methyltransferase) as well as NuRD complexes (histone deacetylases). The KRAB domain tethers these binding pro...

The Role of XPA in DNA Repair

Takahisa Ikegami and Masahiro Shirakawa

XPA, a 273 amino acid protein, is involved in the early stage of the nucleotide excision repair process, by which a variety of DNA lesions are removed from the genome. NMR was used to analyze the structure of the central domain of XPA, which encompasses residues 98 to 219, and contains a zinc c...

A Zinc Ribbon Motif Is Essential for the Formation of Functional Tetrameric Protein Kinase CK2

Odile Filhol, Maria Jose Benitez and Claude Cochet

Protein kinase CK2 plays an essential role in the regulation of many cellular functions. The enzyme is an heterotetrameric complex formed by the association of two catalytic alpha/alpha’ subunits with two regulatory beta subunits. High-resolution structure of the CK2beta subunit revealed the pre...

ZAS Zinc Finger Proteins: The Other ?B-Binding Protein Family

Carl E. Allen and Lai-Chu Wu

The ZAS gene family includes ZAS1, ZAS2, and ZAS3 in mammals as well as Schnurri in Drosophila melanogaster. The ZAS genes encode large proteins with two separate C2H2 zinc finger pairs that independently bind to specific DNA sequences, including the ?beta motif. In vitro experiments have shown...

Sp1 and Huntington’s Disease

Dimitri Krainc

Sp1, a triple C2H2 zinc finger protein, has been studied for more than 2 decades and biochemical features of the protein have been well documented. However, its biological roles in humans are still ambiguous. Recent studies on Huntington’s disease have shown that the mutant huntingtin proteins w...

The DNA-binding Domain of GATA Transcription Factors—A Prototypical Type IV Cys2-Cys2 Zinc Finger

Angela M. Gronenborn

The highly conserved DNA-binding domains (DBDs) of eukaryotic GATA factors comprise one or two zinc binding modules with four cysteines embedded in the sequence Cys-X2-Cys-X17/18-Cys-X2-Cys and an adjacent basic region. The fold has been defined as a class IV zinc finger motif and belongs to th...

Structure and Function of the CBP/p300 TAZ Domains

Roberto N. De Guzman, Maria A. Martinez-Yamout, H. Jane Dyson, and Peter E. Wright

The TAZ (transcriptional adapter zinc binding) domains in the transcriptional coactivators CBP/p300 are zinc-binding motifs that are primarily involved in protein-protein recognition. The activation domains of more than 30 transcription factors have been reported to bind to the TAZ domains, and...

MDM2: RING Finger Protein and Regulator of p53

Liqing Wu and Carl G. Maki

MDM2 is an oncogene that is frequently over-expressed in various human cancers, including sarcomas, glio mas, melanomas, and breast cancers.1 The primary function of MDM2 is to inhibit the activity of the p53 tumor suppressor protein. P53 inhibits cell proliferation in response to DNA damage an...

LIM Domain and Its Binding to Target Proteins

Algirdas Velyvis and Jun Qin

LIM domain is a unique double-zinc finger motif found in a variety of proteins such as homeodomain transcription factors, kinases, and adaptors. The LIM-containing proteins are involved in diverse biological processes including cytoskeleton organization, cell lineage specification and organ deve...

Apoptosis by Zinc Deficiency

Kirsteen H. Maclean

Zinc is an essential trace element for all forms of life. Zinc deficiency affects many systems because of the many roles it encompasses, such as in metabolism (including the activity of more than 300 enzymes), the structure of many proteins and control of genetic expression. Homeostatic regulati...

The Zip Family of Zinc Transporters

David J. Eide

The ZIP family of transporters plays important roles in supplying zinc to metalloproteins. These transporters are found in organisms at all phylogenetic levels including bacteria, fungi, plants, insects, and mammals. They have many conserved sequence elements and most have eight likely transmemb...

The Role of the Ikaros Gene Family in Lymphocyte Development

Pablo Gomez-del Arco, Taku Naito, John Seavitt, Toshimi Yoshida, Christine Williams and Katia Georgopoulos

In many developmental systems, nuclear regulators have been implicated in coupling key events in gene expression with specific cell fate and lineage decisions. In the hemo-lymphoid system, the Ikaros gene family of zinc finger DNA binding factors control lymphocyte specification and homeostasis ...

Yin Yang 1

Huifei Liu, Yang Shi

The transcription factor Yin Yang 1 (YY1) (also known as NF-E1, CP-1 and UCRBP) is a GLI-Kruppel zinc finger protein.1-4YY1 is highly conserved from Xenopus to mammalian YY1 and has been demonstrated to play an essential role in mouse embryonic development and other physiological and pathologic...

The Superfamily of SCAN Domain Containing Zinc Finger Transcription Factors

Tucker Collins and Tara L. Sander

The SCAN domain is a highly conserved 84 residue motif that is found near the N-terminus of a subfamily of C2H2 zinc finger proteins. The SCAN domain, which is also known as the leucine rich region (LeR), functions as a protein interaction domain, mediating self-association or selective associat...

TFIIIA and p43: Binding to 5S Ribosomal RNA

Paul J. Romaniuk

TFIIIA and p43 are multifunctional zinc finger proteins that share a specific affinity for 5S ribosomal RNA. In this chapter I summarize over 25 years of research that highlights the similarities and differences in the RNA binding activity of these two proteins.

Synthetic Zinc Finger Transcription Factors

Nicoletta Corbi, Valentina Libri, Claudio Passananti

The possibility of using designed transcription factors to control gene expression is highly appealing in view of a wide range of promising applications in research and biomedicine. In the last decade, the efforts of several research groups have clarified the molecular interactions between zinc ...

Homing Endonuclease I-TevI: An Atypical Zinc Finger with a Novel Function

Patrick Van Roey, Marlene Belfort and Victoria Derbyshire

I-TevI is a site-specific, sequence-tolerant homing endonuclease encoded by the td intron of bacteriophage T4. The enzyme consists of an N-terminal catalytic domain and a C-terminal DNA-binding domain that are connected by a long, flexible linker. The crystal structure of the DNA-binding domain ...

MOF, an Acetyl Transferase Involved in Dosage Compensation in Drosophila, Uses a CCHC Finger for Substrate Recognition

Asifa Akhtar and Peter B. Becker

The histone acetyltransferase MOF is central to the process of dosage compensation complex in Drosophila, which assures that the transcriptional activity of large parts of the male X chromosome is enhanced by about two-fold. Inactivation of the acetyl transferase activity of MOF is lethal to aff...

RING Finger-B Box-Coiled Coil (RBCC) Proteins As Ubiquitin Ligase in the Control of Protein Degradation and Gene Regulation

Kazuhiro Ikeda, Satoshi Inoue and Masami Muramatsu

The protein family harboring the RING finger motif, defined as a linear array of conserved cysteines and histidines, has grown enormously in the last decade. The members of the family are involved in various biological processes including growth, differentiation, apoptosis, transcription and als...

Ribosomal Zinc Finger Proteins: The Structure and the Function of Yeast YL37a

John Dresios, Yuen-Ling Chan and Ira G. Wool

Zinc finger motifs are common in ribosomal proteins: they are widely distributed in nature, having been found amongst the proteins of both subunits of the ribosomes of all species examined in the three kingdoms; the motif is always of the C2C2 variety and occurs only once in a protein. Despite ...

The Discovery of Zinc Fingers and Their Practical Applications in Gene Regulation: A Personal Account

Aaron Klug

An account is given of the discovery of the classical Cys2His2 (C2H2) zinc finger, arising from biochemical studies on the protein transcription factor IIIA found in Xenopus ooctyes, and of subsequent structural studies on its 3D structure and its interaction with DNA. Each finger is a self-cont...

GAGA: Structural Basis for Single Cys2His2 Zinc Finger-DNA Interaction

G. Marius Clore and James G. Omichinski

The structural basis of sequence specific binding of the Cys2His2 single zinc finger DNA binding domain of the transcription factor GAGA is explored on the basis of the three-dimensional structure of a complex between the minimal DNA binding domain (DBD) of the GAGA factor (GAGA-DBD) and an oli...

The Androgen Receptor and Spinal and Bulbar Muscular Atrophy

F. Piccioni, C.J. Sumner and K.H. Fischbeck

The androgen receptor belongs to the superfamily of nuclear receptors, which are ligand-dependent transcription factors. In the absence of the androgen, the receptor is localized to the cytoplasm where it is associated with heat shock proteins. Upon ligand binding, the receptor translocates into...

Zinc Finger Interactions with Metals and Other Small Molecules

Jay S. Hanas, Jason L. Larabee and James R. Hocker

Zinc fingers encompass a wide variety of compact protein domains that are stabilized by a structural zinc ion which minimally interacts with a cysteine-rich coordination sphere. The selectivity for zinc ion binding is governed by coordinating amino acid side chains and by thermodynamic parameter...

The FYVE Finger: A Phosphoinositide Binding Domain

Harald Stenmark

The FYVE finger is an evolutionarily conserved double-zinc binding domain with structural similarity to RING and PHD fingers. It consists of two ?-hairpins that are stabilized by a C-terminal ?-helix and the coordination of two Zn2+ ions. The most characteristic feature of the FYVE finger is a R...

The Multiple Cellular Functions of TFIIIA

Natalie Kuldell

Transcription factor IIIA (TFIIIA) is a single polypeptide with several distinct functions in the cell. In this chapter I will review the role of TFIIIA in transcription initiation of the 5S rRNA gene. I will also describe the model by which TFIIIA associates with the 5S rRNA itself to regulate ...

TFIIIA: A Sophisticated Zinc Finger Protein

Raymond S. Brown and Jane Flint

Transcription factor IIIA (TFIIIA) is widely regarded as the archetypal zinc finger protein. It is a member of a very large multigene family of eukaryotic DNA-binding proteins. More than two decades of research have been dedicated to understanding its interaction with the 5S ribosomal RNA gene ...

C2H2 Zinc Fingers as DNA Binding Domains

Shiro Iuchi

A great number of C2H2 zinc finger proteins selectively bind to specific DNA sequences and play a critical role in controlling transcription of genes. The specific binding is achieved by zinc finger domains with ??? structure that is formed by tetrahedral binding of Zn2+ io...

Wig-1, A p53-Induced Zinc Finger Protein that Binds Double Stranded RNA

Cristina Mendez-Vidal, Fredrik Hellborg, Margareta T. Wilhelm, Magdalena Tarkowska and Klas G. Wiman

The wig-1 gene (for Wild type p53-Induced Gene 1) is a direct transcriptional target of wild type p53. Wig-1 is a highly conserved unusual nuclear zinc finger protein that binds double stranded RNA. Overexpression of Wig-1 inhibits cell growth. Wig-1 has been implicated in neuronal apopto...

The Role of WT1 in Development and Disease

Sean Bong Lee, Hongjie Li and Ho-Shik Kim

Wilms tumor suppressor gene product WT1 is a Cys2His2 (C2H2 ) zinc finger protein, one of the largest protein families in higher eukaryotes. Since the cloning of WT1 in 1990, we have learned a great deal about the functions of WT1. Now, even greater molecu...

The BTB Domain Zinc Finger Proteins

Gilbert G Privé, Ari Melnick, K Farid Ahmad and Jonathan D. Licht

The BTB/ zinc finger proteins have a wide range of functions in development and homeostasis and a wide range of interactions. The BTB domain appears essential for these proteins to dimerize, facilitate DNA looping, form specific multi-protein structures in the nucleus and interact with co-repre...


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