Finger domain

Parraga, G., et al. Zinc-dependent structure of a single-finger domain of yeast ADRl. Science 241 1489-1492, 1988. 

The ultimate goal of protein engineering is to design an amino acid sequence that will fold into a protein with a predetermined structure and function. Paradoxically, this goal may be easier to achieve than its inverse, the solution of the folding problem. It seems to be simpler to start with a three-dimensional structure and find one of the numerous amino acid sequences that will fold into that structure than to start from an amino acid sequence and predict its three-dimensional structure. We will illustrate this by the design of a stable zinc finger domain that does not require stabilization by zinc. 

Figure 17.15 Schematic diagrams of the main-chain conformations of the second zinc finger domain of Zif 268 (red) and the designed peptide FSD-1 (blue). The zinc finger domain is stabilized by a zinc atom whereas FSD-1 is stabilized by hydrophobic interactions between the p strands and the a helix. (Adapted from B.I. Dahiyat and S.L. Mayo, Science 278 82-87, 1997.)...

Figure 2.20 Schematic representation of a zinc-finger domain from TFIIIA and related proteins. X represents any amino acid conserved amino acids are histidine (H), cysteine (C), tyrosine (Y), phenylalanine (F), and leucine (L).

Maynard, A. T., Huang, M., Rice, W. G., and Covell, D. G. 1998. Reactivity of the HIV-1 nucleocapsid protein p7 zinc finger domains from the perspective of density-functional theory. Proc. Natl. Acad. Sci. USA 95 11578-11583. 

Zinc-finger proteins are also possible targets for bicyclams. All nu-cleocapsid proteins of known strains of retroviruses contain one or two copies of an invariant sequence, Cys-X2-Cys-X4-His-X4-Cys. Proteins with this sequence bind zinc stoichiometrically with dissociation constants of ca. 10-12M (377). Under physiological conditions, a 10-fold excess of EDTA removes only 50% of zinc from the zinc finger domain of HIV-1 nucleocapsid protein (378). 

Fig. 2. Examples of the structures of protein domains and repeats. The images were generated using Molscript (Kraulis, 1991). (A) Immunoglobulin domain (PDB identifier ltlk) (Holden et al1992), (B) A zinc finger domain with coordinated zinc ion (PDB identifienlzaa) (Pavletich and Pabo, 1991). (C) A /3-propeller domain composed of seven WD40 repeats (PDB identifier lgp2) (Wall et al., 1995), (D) An elongated domain of variant leucine-rich repeats (PDB identifienllrv) (Peters et al., 1996).

Borden, K. L., et al.. The solution structure of the RING finger domain from the acute promyelocytic leukaemia proto-oncoprotein PML. EmboJ, 1995, 14(7), 1532-41. 

Meza, J. E., et al.. Mapping the functional domains of BRCAl. Interaction of the ring finger domains of BRCAl and BARDl. / Biol Chem, 1999, 274(9), 5659-65. 

Honda, R. and H. Yasuda, Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase. Oncogene, 2000, 19(11), 1473-6. 

Prakash, The Sacdiaromyces cerevisiae RAD 18 gene encodes a protein that contains potential zinc finger domains for nudeic acid binding and a putative nudeotide binding sequence. Nucleic Acids Res, 1988, 16(14B), 7119-31. 

Fig. 12.6. Domain scheme of selected members of the UIM and GAT family. Domain abbreviations are as follows EH, EpslS-homology domain ENTH, Epsin N-terminal homology domain VHS, N-terminal domain of Vps27, HRS, STAM FVE, EYVE-finger domain ...

D. R., and Sundquist, W. I., Structure and ubiquitin interactions of the conserved zinc finger domain of Npl4, J. Biol. Biol, 2003, 278, 20225. 

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