Journal Issue - Volume 17 Issue 5 (May 2008)
Crystallographic and biochemical studies revealing the structural basis for antizyme inhibitor function
- Shira Albeck, Orly Dym, Tamar Unger, Zohar Snapir, Zippy Bercovich, Chaim Kahana
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073427208 (p 793-802)
Abstract Antizyme inhibitor (AzI) regulates cellular polyamine homeostasis by binding to the polyamine‐induced protein, Antizyme (Az), with greater affinity than ornithine decarboxylase (ODC). AzI is highly homologous to ODC but is not enzymatically active. In order to understand these specific characteristics of AzI and its differences from ODC, we determined the 3D structure of mouse AzI to 2.05 Å resolution. Both AzI and ODC...
N15 Cro and λ Cro: Orthologous DNA‐binding domains with completely different but equally effective homodimer interfaces
- Matthew S. Dubrava, Wendy M. Ingram, Sue A. Roberts, Andrzej Weichsel, William R. Montfort, Matthew H.J. Cordes
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073330808 (p 803-812)
Abstract Bacteriophage Cro proteins bind to target DNA as dimers but do not all dimerize with equal strength, and differ in fold in the region of the dimer interface. We report the structure of the Cro protein from Enterobacteria phage N15 at 1.05 Å resolution. The subunit fold contains five α‐helices and is closely similar to the structure of P22 Cro (1.3 Å backbone room mean square difference over 52 residues), but quite different...
Structure and ion channel activity of the human respiratory syncytial virus (hRSV) small hydrophobic protein transmembrane domain
- Siok Wan Gan, Lifang Ng, Xin Lin, Xiandi Gong, Jaume Torres
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073366208 (p 813-820)
Abstract The small hydrophobic (SH) protein from the human respiratory syncytial virus (hRSV) is a glycoprotein of ∼64 amino acids with one putative α‐helical transmembrane domain. Although SH protein is important for viral infectivity, its exact role during viral infection is not clear. Herein, we have studied the secondary structure, orientation, and oligomerization of the transmembrane domain of SH (SH‐TM) in the presence of...
Structure and dynamics of de novo proteins from a designed superfamily of 4‐helix bundles
- Abigail Go, Seho Kim, Jean Baum, Michael H. Hecht
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073377908 (p 821-832)
Abstract Libraries of de novo proteins provide an opportunity to explore the structural and functional potential of biological molecules that have not been biased by billions of years of evolutionary selection. Given the enormity of sequence space, a rational approach to library design is likely to yield a higher fraction of folded and functional proteins than a stochastic sampling of random sequences. We previously investigated the...
A buried lysine that titrates with a normal p Ka values
- Michael J. Harms, Jamie L. Schlessman, Michael S. Chimenti, Gloria R. Sue, Ana Damjanović, Bertrand García‐Moreno E.
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073397708 (p 833-845)
Abstract Previously we reported that Lys, Asp, and Glu residues at positions 66 and 92 in staphylococcal nuclease (SNase) titrate with pKa values shifted by up to 5 pKa units in the direction that promotes the neutral state. In contrast, the internal Lys‐38 in SNase titrates with a normal pKa. The crystal structure of the L38K variant shows that the side chain of Lys‐38 is buried. The ionizable moiety is ∼7 Å from solvent and ion...
Cysteine 155 plays an important role in the assembly of Mycobacterium tuberculosis FtsZ
- Richa Jaiswal, Dulal Panda
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.083452008 (p 846-854)
Abstract The assembly of FtsZ plays an important role in bacterial cell division. Mycobacterium tuberculosis FtsZ (MtbFtsZ) has a single cysteine residue at position 155. We have investigated the role of the lone cysteine residue in the assembly of MtbFtsZ using different complimentary approaches, namely chemical modification by a thiol‐specific reagent 5,5′‐dithiobis‐(2‐nitrobenzoic acid) (DTNB) or a cysteine‐chelating agent HgCl2, and...
Structural effects of Parkinson's disease linked DJ‐1 mutations
- Gaetano Malgieri, David Eliezer
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073411608 (p 855-868)
Abstract Mutations in the protein DJ‐1 are associated with familial forms of Parkinson's disease, indicating that DJ‐1 may be involved in pathways related to the etiology of this disorder. Here we have used solution state NMR and circular dichroism spectroscopies to evaluate the extent of structural perturbations associated with five different Parkinson's disease linked DJ‐1mutations: L166P, E64D, M26I, A104T, and D149A. Comparison...
Structure and ligand binding of the soluble domain of a Thermotoga maritima membrane protein of unknown function TM1634
- Clare J. McCleverty, Linda Columbus, Andreas Kreusch, Scott A. Lesley
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.083432208 (p 869-877)
Abstract As a part of the Joint Center for Structural Genomics (JCSG) biological targets, the structures of soluble domains of membrane proteins from Thermotoga maritima were pursued. Here, we report the crystal structure of the soluble domain of TM1634, a putative membrane protein of 128 residues (15.1 kDa) and unknown function. The soluble domain of TM1634 is an α‐helical dimer that contains a single tetratrico peptide repeat...
Structural basis for the NAD‐hydrolysis mechanism and the ARTT‐loop plasticity of C3 exoenzymes
- Julie Ménétrey, Gilles Flatau, Patrice Boquet, André Ménez, Enrico A. Stura
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073398508 (p 878-886)
Abstract C3‐like exoenzymes are ADP‐ribosyltransferases that specifically modify some Rho GTPase proteins, leading to their sequestration in the cytoplasm, and thus inhibiting their regulatory activity on the actin cytoskeleton. This modification process goes through three sequential steps involving NAD‐hydrolysis, Rho recognition, and binding, leading to Rho ADP‐ribosylation. Independently, three distinct residues within the ARTT...
Molecular determinants of the aggregation behavior of α‐ and β‐synuclein
- Robert C. Rivers, Janet R. Kumita, Gian Gaetano Tartaglia, Matthew M. Dedmon, Amol Pawar, Michele Vendruscolo, Christopher M. Dobson, John Christodoulou
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073181508 (p 887-898)
Abstract α‐ and β‐synuclein are closely related proteins, the first of which is associated with deposits formed in neurodegenerative conditions such as Parkinson's disease while the second appears to have no relationship to any such disorders. The aggregation behavior of α‐ and β‐synuclein as well as a series of chimeric variants were compared by exploring the structural transitions that occur in the presence of a widely used lipid...
RDC‐assisted modeling of symmetric protein homo‐oligomers
- Xu Wang, Sonal Bansal, Mei Jiang, James H. Prestegard
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073395108 (p 899-907)
Abstract Protein oligomerization serves an important function in biological processes, yet solving structures of protein oligomers has always been a challenge. For solution NMR, the challenge arises both from the increased size of these systems and, in the case of homo‐oligomers, from ambiguities in assignment of intra‐ as opposed to intersubunit NOEs. In this study, we present a residual dipolar coupling (RDC)‐assisted method for...
Miranda cargo‐binding domain forms an elongated coiled‐coil homodimer in solution: Implications for asymmetric cell division in Drosophila
- Mohammad S. Yousef, Hironari Kamikubo, Mikio Kataoka, Ryuichi Kato, Soichi Wakatsuki
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.083431408 (p 908-917)
Abstract Miranda is a multidomain adaptor protein involved in neuroblast asymmetric division in Drosophila melanogaster. The central domain of Miranda is necessary for cargo binding of the neural transcription factor Prospero, the Prospero‐mRNA carrier Staufen, and the tumor suppressor Brat. Here, we report the first solution structure of Miranda central “cargo‐binding” domain (residues 460–660) using small‐angle X‐ray scattering. Ab initio...
Correspondences between low‐energy modes in enzymes: Dynamics‐based alignment of enzymatic functional families
- Andrea Zen, Vincenzo Carnevale, Arthur M. Lesk, Cristian Micheletti
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073390208 (p 918-929)
Abstract Proteins that show similarity in their equilibrium dynamics can be aligned by identifying regions that undergo similar concerted movements. These movements are computed from protein native structures using coarse‐grained elastic network models. We show the existence of common large‐scale movements in enzymes selected from the main functional and structural classes. Alignment via dynamics does not require prior detection of...
Transmembrane helices that form two opposite homodimeric interactions: An asparagine scan study of αM and β2 integrins
- Krupakar Parthasarathy, Xin Lin, Suet Mien Tan, S.K. Alex Law, Jaume Torres
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.073234208 (p 930-938)
Abstract Integrins are α/β heterodimers, but recent in vitro and in vivo experiments also suggest an ability to associate through their transmembrane domains to form homomeric interactions. While the results of some in vitro experiments are consistent with an interaction mediated by a GxxxG‐like motif, homo‐oligomers observed after in vivo cross‐linking are consistent with an almost opposite helix–helix interface. We have shown...
Conformational gating of dimannose binding to the antiviral protein cyanovirin revealed from the crystal structure at 1.35 Å resolution
- Raimund Fromme, Zivile Katiliene, Petra Fromme, Giovanna Ghirlanda
- Published in Wiley Interscience on Jan 02, 2009
- DOI: 10.1110/ps.083472808 (p 939-944)
Abstract Cyanovirin (CV‐N) is a small lectin with potent HIV neutralization activity, which could be exploited for a mucosal defense against HIV infection. The wild‐type (wt) protein binds with high affinity to mannose‐rich oligosaccharides on the surface of gp120 through two quasi‐symmetric sites, located in domains A and B. We recently reported on a mutant of CV‐N that contained a single functional mannose‐binding site, domain B,...




