Journal Issue - Volume 19 Issue 7 (July 2010)
In this issue
- Published in Wiley Interscience on Jun 23, 2010
- DOI: 10.1002/pro.442 (p )
Peripatetic proteins
- Brian W. Matthews
- Published in Wiley Interscience on May 24, 2010
- DOI: 10.1002/pro.422 (p 1279-1280)
Thioesterases: A new perspective based on their primary and tertiary structures
- David C. Cantu, Yingfei Chen, Peter J. Reilly
- Published in Wiley Interscience on May 17, 2010
- DOI: 10.1002/pro.417 (p 1281-1295)
Abstract Thioesterases (TEs) are classified into EC 3.1.2.1 through EC 3.1.2.27 based on their activities on different substrates, with many remaining unclassified (EC 3.1.2.–). Analysis of primary and tertiary structures of known TEs casts a new light on this enzyme group. We used strong primary sequence conservation based on experimentally proved proteins as the main criterion, followed by verification with tertiary structure...
Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation
- A. D. Wilkins, R. Lua, S. Erdin, R. M. Ward, O. Lichtarge
- Published in Wiley Interscience on Apr 27, 2010
- DOI: 10.1002/pro.406 (p 1296-1311)
Abstract Protein functional sites control most biological processes and are important targets for drug design and protein engineering. To characterize them, the evolutionary trace (ET) ranks the relative importance of residues according to their evolutionary variations. Generally, top‐ranked residues cluster spatially to define evolutionary hotspots that predict functional sites in structures. Here, various functions that measure...
Gene optimization mechanisms: A multi‐gene study reveals a high success rate of full‐length human proteins expressed in Escherichia coli
- Barbara Maertens, Anne Spriestersbach, Uritza von Groll, Udo Roth, Jan Kubicek, Michael Gerrits, Marcus Graf, Michael Liss, Daniela Daubert, Ralf Wagner, Frank Schäfer
- Published in Wiley Interscience on May 03, 2010
- DOI: 10.1002/pro.408 (p 1312-1326)
Abstract The genetic code is universal, but recombinant protein expression in heterologous systems is often hampered by divergent codon usage. Here, we demonstrate that reprogramming by standardized multi‐parameter gene optimization software and de novo gene synthesis is a suitable general strategy to improve heterologous protein expression. This study compares expression levels of 94 full‐length human wt and sequence‐optimized genes coding for...
Dimerization of the hepatitis C virus nonstructural protein 4B depends on the integrity of an aminoterminal basic leucine zipper
- Martin‐Walter Welker, Christoph Welsch, Aline Meyer, Iris Antes, Mario Albrecht, Nicole Forestier, Bernd Kronenberger, Thomas Lengauer, Albrecht Piiper, Stefan Zeuzem, Christoph Sarrazin
- Published in Wiley Interscience on May 03, 2010
- DOI: 10.1002/pro.409 (p 1327-1336)
Abstract The hepatitis C virus (HCV) nonstructural (NS) protein 4B is known for protein–protein interactions with virus and host cell factors. Only little is known about the corresponding protein binding sites and underlying molecular mechanisms. Recently, we have predicted a putative basic leucine zipper (bZIP) motif within the aminoterminal part of NS4B. The aim of this study was to investigate the importance of this NS4B bZIP...
The crystal structure of the Y140F mutant of ADP‐
L ‐ glycero ‐D ‐ manno ‐heptose 6‐epimerase bound to ADP‐β‐D ‐mannose suggests a one base mechanism- Thomas Kowatz, James P. Morrison, Martin E. Tanner, James H. Naismith
- Published in Wiley Interscience on May 05, 2010
- DOI: 10.1002/pro.410 (p 1337-1343)
Abstract Bacteria synthesize a wide array of unusual carbohydrate molecules, which they use in a variety of ways. The carbohydrate L‐glycero‐D‐manno‐heptose is an important component of lipopolysaccharide and is synthesized in a complex series of enzymatic steps. One step involves the epimerization at the C6″ position converting ADP‐D‐glycero‐D‐manno‐heptose into ADP‐L‐glycero‐D‐manno‐heptose. The enzyme responsible is a member of the short...
Export of a hyperexpressed mammalian globular cytochrome b 5 precursor in Escherichia coli is dramatically affected by the nature of the amino acid flanking the secretory signal sequence cleavage bond
- Naheed N. Kaderbhai, Khalil Ahmed, Mustak A. Kaderbhai
- Published in Wiley Interscience on May 05, 2010
- DOI: 10.1002/pro.411 (p 1344-1353)
Abstract A chimeric mammalian globular cytochrome b5 fused to Escherichia coli alkaline phosphatase signal sequence (SS) was used as a model probe to investigate the influence of substituting each one of the standard 20 amino acids at its N‐terminus on the Sec‐dependent export of the precursor to the periplasmic space of E. coli. Substituting the native Met+1 of the passenger protein flanking the SS with any one of the remaining 19 amino acids...
Structure of the dimerization domain of DiGeorge Critical Region 8
- Rachel Senturia, Michael Faller, Sheng Yin, Joseph A. Loo, Duilio Cascio, Michael R. Sawaya, Daniel Hwang, Robert T. Clubb, Feng Guo
- Published in Wiley Interscience on May 07, 2010
- DOI: 10.1002/pro.414 (p 1354-1365)
Abstract Maturation of microRNAs (miRNAs, ∼22nt) from long primary transcripts [primary miRNAs (pri‐miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA‐binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme‐bound...
How sequence directs bending in tropomyosin and other two‐stranded alpha‐helical coiled coils
- Jerry H. Brown
- Published in Wiley Interscience on May 07, 2010
- DOI: 10.1002/pro.415 (p 1366-1375)
Abstract A quantitative analysis of the direction of bending of two‐stranded alpha‐helical coiled coils in crystal structures has been carried out to help determine how the amino acid sequence of the coiled coil influences its shape and function. Change in the axial staggering of the coiled coil, occurring at the boundaries of either clusters of core alanines in tropomyosin or of clusters of core bulky residues in the myosin rod,...
Functional dissection of an intrinsically disordered protein: Understanding the roles of different domains of Knr4 protein in protein–protein interactions
- Adilia Dagkessamanskaia, Fabien Durand, Vladimir N. Uversky, Matteo Binda, Frédéric Lopez, Karim El Azzouzi, Jean Marie Francois, Hélène Martin‐Yken
- Published in Wiley Interscience on May 17, 2010
- DOI: 10.1002/pro.418 (p 1376-1385)
Abstract Knr4, recently characterized as an intrinsically disordered Saccharomyces cerevisiae protein, participates in cell wall formation and cell cycle regulation. It is constituted of a functional central globular core flanked by a poorly structured N‐terminal and large natively unfolded C‐terminal domains. Up to now, about 30 different proteins have been reported to physically interact with Knr4. Here, we used an in vivo two‐hybrid system...
DE‐loop mutations affect β2 microglobulin stability, oligomerization, and the low‐pH unfolded form
- Carlo Santambrogio, Stefano Ricagno, Matteo Colombo, Alberto Barbiroli, Francesco Bonomi, Vittorio Bellotti, Martino Bolognesi, Rita Grandori
- Published in Wiley Interscience on May 17, 2010
- DOI: 10.1002/pro.419 (p 1386-1394)
Abstract β2 microglobulin (β2m) is the light chain of class‐I major histocompatibility complex (MHC‐I). Its accumulation in the blood of patients affected by kidney failure leads to amyloid deposition around skeletal joints and bones, a severe condition known as Dialysis Related Amyloidosis (DRA). In an effort to dissect the structural determinants of β2m aggregation, several β2m mutants have been previously studied. Among these,...
New surface contacts formed upon reductive lysine methylation: Improving the probability of protein crystallization
- Pawel Sledz, Heping Zheng, Krzysztof Murzyn, Maksymilian Chruszcz, Matthew D. Zimmerman, Mahendra D. Chordia, Andrzej Joachimiak, Wladek Minor
- Published in Wiley Interscience on May 17, 2010
- DOI: 10.1002/pro.420 (p 1395-1404)
Abstract Surface lysine methylation (SLM) is a technique for improving the rate of success of protein crystallization by chemically methylating lysine residues. The exact mechanism by which SLM enhances crystallization is still not clear. To study these mechanisms, and to analyze the conditions where SLM will provide the optimal benefits for rescuing failed crystallization experiments, we compared 40 protein structures containing...
The transcription repressor NmrA is subject to proteolysis by three Aspergillus nidulans proteases
- Xiao Zhao, Samantha L. Hume, Christopher Johnson, Paul Thompson, Junyong Huang, Joe Gray, Heather K. Lamb, Alastair R. Hawkins
- Published in Wiley Interscience on May 17, 2010
- DOI: 10.1002/pro.421 (p 1405-1419)
Abstract The role of specific cleavage of transcription repressor proteins by proteases and how this may be related to the emerging theme of dinucleotides as cellular signaling molecules is poorly characterized. The transcription repressor NmrA of Aspergillus nidulans discriminates between oxidized and reduced dinucleotides, however, dinucleotide binding has no effect on its interaction with the zinc finger in the transcription activator AreA....
Automated electron‐density sampling reveals widespread conformational polymorphism in proteins
- P. Therese Lang, Ho‐Leung Ng, James S. Fraser, Jacob E. Corn, Nathaniel Echols, Mark Sales, James M. Holton, Tom Alber
- Published in Wiley Interscience on May 24, 2010
- DOI: 10.1002/pro.423 (p 1420-1431)
Abstract Although proteins populate large structural ensembles, X‐ray diffraction data are traditionally interpreted using a single model. To search for evidence of alternate conformers, we developed a program, Ringer, which systematically samples electron density around the dihedral angles of protein side chains. In a diverse set of 402 structures, Ringer identified weak, nonrandom electron‐density features that suggest of the...




