Journal Issue - Volume 19 Issue 4 (April 2010)
In this issue
- Published in Wiley Interscience on Mar 24, 2010
- DOI: 10.1002/pro.373 (p )
The proline‐rich domain of TonB possesses an extended polyproline II‐like conformation of sufficient length to span the periplasm of Gram‐negative bacteria
- Silvia Domingo Köhler, Annemarie Weber, S. Peter Howard, Wolfram Welte, Malte Drescher
- Published in Wiley Interscience on Jan 21, 2010
- DOI: 10.1002/pro.345 (p 625-630)
Abstract TonB from Escherichia coli and its homologues are critical for the uptake of siderophores through the outer membrane of Gram‐negative bacteria using chemiosmotic energy. When different models for the mechanism of TonB mediated energy transfer from the inner to the outer membrane are discussed, one of the key questions is whether TonB spans the periplasm. In this article, we use long range distance measurements by spin‐label...
Lessons from the lysozyme of phage T4
- Walter A. Baase, Lijun Liu, Dale E. Tronrud, Brian W. Matthews
- Published in Wiley Interscience on Jan 21, 2010
- DOI: 10.1002/pro.344 (p 631-641)
Abstract An overview is presented of some of the major insights that have come from studies of the structure, stability, and folding of T4 phage lysozyme. A major purpose of this review is to provide the reader with a complete tabulation of all of the variants that have been characterized, including melting temperatures, crystallographic data, Protein Data Bank access codes, and references to the original literature. The greatest...
Small‐angle scattering for structural biology—Expanding the frontier while avoiding the pitfalls
- David A. Jacques, Jill Trewhella
- Published in Wiley Interscience on Jan 29, 2010
- DOI: 10.1002/pro.351 (p 642-657)
Abstract The last decade has seen a dramatic increase in the use of small‐angle scattering for the study of biological macromolecules in solution. The drive for more complete structural characterization of proteins and their interactions, coupled with the increasing availability of instrumentation and easy‐to‐use software for data analysis and interpretation, is expanding the utility of the technique beyond the domain of the...
The adapter protein Nck: Role of individual SH3 and SH2 binding modules for protein interactions in T lymphocytes
- Marcus Lettau, Jennifer Pieper, Alyn Gerneth, Beate Lengl‐Janßen, Matthias Voss, Andreas Linkermann, Hendrik Schmidt, Christoph Gelhaus, Matthias Leippe, Dieter Kabelitz, Ottmar Janssen
- Published in Wiley Interscience on Jan 15, 2010
- DOI: 10.1002/pro.334 (p 658-669)
Abstract Nck is a ubiquitously expressed, primarily cytosolic adapter protein consisting of one SH2 domain and three SH3 domains. It links receptor and nonreceptor tyrosine kinases to actin cytoskeleton reorganizing proteins. In T lymphocytes, Nck is a crucial component of signaling pathways for T cell activation and effector function. It recruits actin remodeling proteins to T cell receptor (TCR)‐associated activation clusters and...
Cysteine‐free rop: A four‐helix bundle core mutant has wild‐type stability and structure but dramatically different unfolding kinetics
- Sanjay B. Hari, Chang Byeon, Jason J. Lavinder, Thomas J. Magliery
- Published in Wiley Interscience on Jan 21, 2010
- DOI: 10.1002/pro.342 (p 670-679)
Abstract Cysteine residues can complicate the folding and storage of proteins due to improper formation of disulfide bonds or oxidation of residues that are natively reduced. Wild‐type Rop is a homodimeric four‐helix bundle protein and an important model for protein design in the understanding of protein stability, structure and folding kinetics. In the native state, Rop has two buried, reduced cysteine residues in its core, but...
Critical biophysical properties in the Pseudomonas aeruginosa efflux gene regulator MexR are targeted by mutations conferring multidrug resistance
- Cecilia Andrésen, Shah Jalal, Daniel Aili, Yi Wang, Sohidul Islam, Anngelica Jarl, Bo Liedberg, Bengt Wretlind, Lars‐Göran Mårtensson, Maria Sunnerhagen
- Published in Wiley Interscience on Jan 21, 2010
- DOI: 10.1002/pro.343 (p 680-692)
Abstract The self‐assembling MexA‐MexB‐OprM efflux pump system, encoded by the mexO operon, contributes to facile resistance of Pseudomonas aeruginosa by actively extruding multiple antimicrobials. MexR negatively regulates the mexO operon, comprising two adjacent MexR binding sites, and is as such highly targeted by mutations that confer multidrug resistance (MDR). To understand how MDR mutations impair MexR function, we studied MexR‐wt as well as a...
Structural basis for unfolding pathway‐dependent stability of proteins: Vectorial unfolding versus global unfolding
- Keisuke Yagawa, Koji Yamano, Takaomi Oguro, Masahiro Maeda, Takehiro Sato, Takaki Momose, Shin Kawano, Toshiya Endo
- Published in Wiley Interscience on Jan 21, 2010
- DOI: 10.1002/pro.346 (p 693-702)
Abstract Point mutations in proteins can have different effects on protein stability depending on the mechanism of unfolding. In the most interesting case of I27, the Ig‐like module of the muscle protein titin, one point mutation (Y9P) yields opposite effects on protein stability during denaturant‐induced “global unfolding” versus “vectorial unfolding” by mechanical pulling force or cellular unfolding systems. Here, we assessed the...
Drug binding and resistance mechanism of KIT tyrosine kinase revealed by hydrogen/deuterium exchange FTICR mass spectrometry
- Hui‐Min Zhang, Xiu Yu, Michael J. Greig, Ketan S. Gajiwala, Joe C. Wu, Wade Diehl, Elizabeth A. Lunney, Mark R. Emmett, Alan G. Marshall
- Published in Wiley Interscience on Jan 21, 2010
- DOI: 10.1002/pro.347 (p 703-715)
Abstract Mutations of the receptor tyrosine kinase KIT are linked to certain cancers such as gastrointestinal stromal tumors (GISTs). Biophysical, biochemical, and structural studies have provided insight into the molecular basis of resistance to the KIT inhibitors, imatinib and sunitinib. Here, solution‐phase hydrogen/deuterium exchange (HDX) and direct binding mass spectrometry experiments provide a link between static structure...
Structural and dynamical characterization of tubular HIV‐1 capsid protein assemblies by solid state nuclear magnetic resonance and electron microscopy
- Bo Chen, Robert Tycko
- Published in Wiley Interscience on Jan 21, 2010
- DOI: 10.1002/pro.348 (p 716-730)
Abstract The wild‐type HIV‐1 capsid protein (CA) self‐assembles in vitro into tubular structures at high ionic strength. We report solid state nuclear magnetic resonance (NMR) and electron microscopy measurements on these tubular CA assemblies, which are believed to contain a triangular lattice of hexameric CA proteins that is similar or identical to the lattice of capsids in intact HIV‐1. Mass‐per‐length values of CA assemblies determined by...
Unusual binding interactions in PDZ domain crystal structures help explain binding mechanisms
- Jonathan M. Elkins, Carina Gileadi, Leela Shrestha, Claire Phillips, Jing Wang, João R.C. Muniz, Declan A. Doyle
- Published in Wiley Interscience on Jan 29, 2010
- DOI: 10.1002/pro.349 (p 731-741)
Abstract PDZ domains most commonly bind the C‐terminus of their protein targets. Typically the C‐terminal four residues of the protein target are considered as the binding motif, particularly the C‐terminal residue (P0) and third‐last residue (P‐2) that form the major contacts with the PDZ domain's “binding groove”. We solved crystal structures of seven human PDZ domains, including five of the seven PDLIM family members. The...
Mining protein dynamics from sets of crystal structures using “consensus structures”
- Gerard J. P. van Westen, Jörg K. Wegner, Andreas Bender, Adriaan P. IJzerman, Herman W. T. van Vlijmen
- Published in Wiley Interscience on Jan 29, 2010
- DOI: 10.1002/pro.350 (p 742-752)
Abstract In this work, we describe two novel approaches to utilize the dynamic structure information implicitly contained in large crystal structure data sets. The first approach visualizes both consistent as well as variable ligand‐induced changes in ligand‐bound compared with apo protein crystal structures. For this purpose, information was mined from B‐factors and ligand‐induced residue displacements in multiple crystal...
Mutations within a human IgG2 antibody form distinct and homogeneous disulfide isomers but do not affect Fc gamma receptor or C1q binding
- Sandra Lightle, Serdar Aykent, Nathan Lacher, Vesselin Mitaksov, Kristine Wells, James Zobel, Theodore Oliphant
- Published in Wiley Interscience on Jan 29, 2010
- DOI: 10.1002/pro.352 (p 753-762)
Abstract Human IgG2 antibodies may exist in at least three distinct structural isomers due to disulfide shuffling within the upper hinge region. Antibody interactions with Fc gamma receptors and the complement component C1q contribute to immune effector functions. These interactions could be impacted by the accessibility and structure of the hinge region. To examine the role structural isomers may have on effector functions, a...
An enriched structural kinase database to enable kinome‐wide structure‐based analyses and drug discovery
- Natasja Brooijmans, Yu‐Wei Chang, Dominick Mobilio, Rajiah A. Denny, Christine Humblet
- Published in Wiley Interscience on Feb 04, 2010
- DOI: 10.1002/pro.355 (p 763-774)
Abstract The development of a kinase structural database, the kinase knowledge base (KKB), is described. It covers all human kinase domain structures that have been deposited in the Protein Data Bank. All structures are renumbered using a common scheme, which enables efficient cross‐comparisons and multiple queries of interest to the kinase field. The common numbering scheme is also used to automatically annotate conserved residues...
Noncollagenous region of the streptococcal collagen‐like protein is a trimerization domain that supports refolding of adjacent homologous and heterologous collagenous domains
- Zhuoxin Yu, Oleg Mirochnitchenko, Chunying Xu, Ayumi Yoshizumi, Barbara Brodsky, Masayori Inouye
- Published in Wiley Interscience on Feb 16, 2010
- DOI: 10.1002/pro.356 (p 775-785)
Abstract Proper folding of the (Gly‐Xaa‐Yaa)n sequence of animal collagens requires adjacent N‐ or C‐terminal noncollagenous trimerization domains which often contain coiled‐coil or beta sheet structure. Collagen‐like proteins have been found recently in a number of bacteria, but little is known about their folding mechanism. The Scl2 collagen‐like protein from Streptococcus pyogenes has an N‐terminal globular domain, designated Vsp, adjacent...




