Abstract:
:Membrane proteins are unique, in that they can function properly only when they are bound to cellular membranes in a distinct manner. Therefore, positioning of membrane proteins with respect to the membrane is required in addition to the three-dimensional structures in order to understand their detailed molecular mechanisms. Atomic-resolution structures of membrane proteins that have been determined to date provide the atom coordinates in arbitrary coordinate systems with no relation to the membrane and therefore provide little or no information on how the protein would interact with the membrane. This is especially true for peripheral membrane proteins, because they, unlike integral proteins, are devoid of well-defined hydrophobic transmembrane domains. Here, we present a novel technique for determination of the configuration of a protein-membrane complex that involves protein ligation, segmental isotope labeling, polarized infrared spectroscopy, membrane depth-dependent fluorescence quenching, and analytical geometry algorithms. We have applied this approach to determine the structure of a membrane-bound phospholipase A2. Our results provide an unprecedented structure of a membrane-bound protein in which the z-coordinate of each atom is the distance from the membrane center and therefore allows precise location of each amino acid relative to the membrane. Given the functional significance of the orientation and location of membrane-bound proteins with respect to the membrane, we propose to specify this structural feature as the "quinary" structure of membrane proteins.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Tatulian SA,Qin S,Pande AH,He Xdoi
10.1016/j.jmb.2005.06.080keywords:
subject
Has Abstractpub_date
2005-09-02 00:00:00pages
939-47issue
5eissn
0022-2836issn
1089-8638pii
S0022-2836(05)00759-Xjournal_volume
351pub_type
杂志文章abstract::Vascular smooth muscle cell hypertrophy and proliferation may participate in the pathophysiology of cardiovascular disease. The analysis of changes in gene expression in vascular smooth muscle cells is crucial to the understanding of the molecular biology of cardiovascular disease. An effective method for analysis of ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1998.1768
更新日期:1998-06-05 00:00:00
abstract::Analysis of the conformational differences between the oxy and deoxy forms of hemoglobin is complicated by shifting coordinate systems and correlated motions between different parts of the molecule. Methods independent of any frame of reference were used to study the differences in structure between the oxy and deoxy ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.1087
更新日期:1997-07-25 00:00:00
abstract::High amphiphilicity is a hallmark of interfacial helices in membrane proteins and membrane-active peptides, such as toxins and antimicrobial peptides. Although there is general agreement that amphiphilicity is important for membrane-interface binding, an unanswered question is its importance relative to simple hydroph...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2007.05.016
更新日期:2007-07-13 00:00:00
abstract::We have identified the recognition sequence for the Citrobacter freundii restriction endonuclease CfrA, a member of the A-family of type I R-M enzymes. This bipartite target sequence differs in both its components from those of other type I enzymes. We determined the nucleotide sequence of its specificity gene (hsdS) ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(89)90001-6
更新日期:1989-10-05 00:00:00
abstract::The amino acid sequence of the rod portion of talin contains strong periodic patterns with a long period of 32 to 34 residues superimposed on short periods of 7 and 7/2 residues. The rod includes 50 to 60 copies of an irregular repeated motif approximately 34 residues long. The motif itself consists of three sections:...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1994.1081
更新日期:1994-01-28 00:00:00
abstract::Rearrangement of actin filaments by polymerization, depolymerization, and severing is important for cell locomotion, membrane trafficking, and many other cellular functions. Cofilin and actin-interacting protein 1 (AIP1; also known as WDR1) are evolutionally conserved proteins that cooperatively sever actin filaments....
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2018.11.010
更新日期:2019-01-18 00:00:00
abstract::Phosphosignaling through pSer/pThr/pTyr is emerging as a common signaling mechanism in prokaryotes. The human pathogen Staphylococcus aureus produces two low-molecular-weight protein tyrosine phosphatases (PTPs), PtpA and PtpB, with unknown functions. To provide the structural context for understanding PtpA function a...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2011.08.015
更新日期:2011-10-14 00:00:00
abstract::The mechanisms for de novo protein folding differ significantly between bacteria and eukaryotes, as evidenced by the often observed poor yields of native eukaryotic proteins upon recombinant production in bacterial systems. Polypeptide synthesis rates are faster in bacteria than in eukaryotes, but the effects of gener...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2009.12.042
更新日期:2010-03-12 00:00:00
abstract::Clinical studies have revealed that mutations in the ventricular myosin regulatory light chain (RLC) lead to the development of familial hypertrophic cardiomyopathy (FHC), an autosomal dominant disease characterized by left ventricular hypertrophy, myofibrillar disarray and sudden cardiac death. While mutations in oth...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.06.018
更新日期:2006-08-11 00:00:00
abstract::The preparation of hybrid histone octamers with wheat histone H2A variants replacing chicken H2A in the chicken octamer is described. The fidelity of the reconstituted hybrid octamers was confirmed by dimethyl suberimidate cross-linking. Polyglutamic-acid-mediated assembly of these octamers on long DNA and subsequent ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(91)90268-b
更新日期:1991-04-20 00:00:00
abstract::Enzymes exhibit a strong long-range evolutionary constraint that extends from their catalytic site and affects even distant sites, where site-specific evolutionary rate increases monotonically with distance. While protein-protein sites in enzymes were previously shown to induce only a weak conservation gradient, a com...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2019.07.019
更新日期:2019-09-06 00:00:00
abstract::Designed retroaldolases have utilized a nucleophilic lysine to promote carbon-carbon bond cleavage of β-hydroxy-ketones via a covalent Schiff base intermediate. Previous computational designs have incorporated a water molecule to facilitate formation and breakdown of the carbinolamine intermediate to give the Schiff b...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2013.10.012
更新日期:2014-01-09 00:00:00
abstract::Eicosanoids are potent lipid mediators involved in central physiological processes such as hemostasis, renal function and parturition. When formed in excess, eicosanoids become critical players in a range of pathological conditions, in particular pain, fever, arthritis, asthma, cardiovascular disease and cancer. Eicos...
journal_title:Journal of molecular biology
pub_type: 杂志文章,评审
doi:10.1016/j.jmb.2020.07.020
更新日期:2020-08-21 00:00:00
abstract::G protein coupled receptors (GPCRs) are integral membrane proteins that mediate cellular responses to a wide variety of extracellular signals. However, the structural basis for activation of this class of receptors by ligand binding is not well understood. We report here the use of a systematic genetic protocol for id...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1996.0816
更新日期:1997-02-28 00:00:00
abstract::To investigate the relationships between sequence conservation, protein stability, and protein function, we have measured the thermodynamic stability, folding kinetics, and in vitro peptide-binding activity of a large number of single-site substitutions in the hydrophobic core of the Fyn SH3 domain. Comparison of thes...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2003.08.035
更新日期:2003-10-24 00:00:00
abstract::We identified the predominant 5' ends of an mRNA in Escherichia coli to the exact nucleotides. There are four such ends of lac mRNA in fully induced cells. About 70% of the molecules have the reported major in vitro end, A-A-U-U-G (at +1), which is located 38 nucleotides before the A-U-G translation start. Another 15%...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(85)90342-0
更新日期:1985-03-20 00:00:00
abstract::Binding of the TATA-binding protein (TBP) to the "TATA" sequences present in the promoters of eukaryotic class II genes is the first step in the sequential assembly of transcription pre-initiation complexes. Myriad structural changes, including severe bending of the DNA, accompany TBP-TATA complex formation. A detaile...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1999.2835
更新日期:1999-06-25 00:00:00
abstract::Dysregulation of hepatocyte growth factor (HGF)-induced signaling via its receptor tyrosine kinase Met results in tumor progression and metastasis. To initiate signaling, pro-HGF must be proteolytically activated to reveal a secondary Met binding site within the serine protease-like beta-chain of HGF. Although HGF/Met...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2008.09.091
更新日期:2009-01-09 00:00:00
abstract::We previously described the use of a phage-displayed library of random hexapeptides to define and localise the epitope on the human tumor suppressor protein p53 recognised by the monoclonal antibody PAb240. Here we have extended these results to a further eight anti-p53 monoclonal antibodies and to two further librari...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1995.0202
更新日期:1995-04-21 00:00:00
abstract::The Escherichia coli cyclic AMP receptor protein, CRP, induces transcription at Class II CRP-dependent promoters by making three different activatory contacts with different surfaces of holo RNA polymerase. One contact surface of CRP, known as Activating Region 3 (AR3), is functional in the downstream subunit of the C...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.2000.3737
更新日期:2000-06-02 00:00:00
abstract::Automated protein redesign, as implemented in the program ORBIT, was used to redesign the core of phage T4 lysozyme. A total of 26 buried or partially buried sites in the C-terminal domain were allowed to vary both their sequence and side-chain conformation while the backbone and non-selected side-chains remained fixe...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/s0022-2836(03)00856-8
更新日期:2003-09-19 00:00:00
abstract::We previously reported that in Micrococcus luteus, a Gram-positive eubacterium with high genomic G + C content, certain codons ending with A did not appear in coding frames, including termination sites, and tRNAs that translate these codons were not detected. These facts suggest that at least some of them are unassign...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1993.1125
更新日期:1993-03-05 00:00:00
abstract::Eukaryotes have several highly conserved actin-binding proteins that crosslink filamentous actin into compact ordered bundles present in distinct cytoskeletal processes, including microvilli, stereocilia and filopodia. Fascin is an actin-binding protein that is present predominantly in filopodia, which are believed to...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2010.04.043
更新日期:2010-07-16 00:00:00
abstract::Crystals of a chymotrypsin inhibitor from Erythrina caffra seeds have been grown out of lithium sulfate, by the hanging drop method of vapor diffusion. The crystals belong to the rhombohedral space group R32, with a = 67.2 A and alpha = 99.4 degrees, and diffract to 3 A resolution. ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/0022-2836(90)90300-B
更新日期:1990-03-05 00:00:00
abstract::The lectin from the mushroom Psathyrella velutina recognises specifically N-acetylglucosamine and N-acetylneuraminic acid containing glycans. The crystal structure of the 401 amino acid residue lectin shows that it adopts a very regular seven-bladed beta-propeller fold with the N-terminal region tucked into the centra...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2006.01.066
更新日期:2006-04-14 00:00:00
abstract::We investigated the role of a partially folded intermediate that transiently accumulates during lysozyme folding. Previous studies had shown that the partially folded intermediate is located on a slow-folding pathway and that an additional fast direct pathway from the unfolded state to the native state exists. Kinetic...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1997.1030
更新日期:1997-07-11 00:00:00
abstract::Proteolysis of rat liver chromatin by the Arg-C peptidase, clostripain, is characterized by a progressive fragmentation of the N-terminal segments of the four core histones H2A, H2B, H3 and H4, until a well-defined limit digest is reached. This work addresses the case of histone H4. Two intermediate proteolytic sites ...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1006/jmbi.1994.1629
更新日期:1994-10-14 00:00:00
abstract::Our present understanding of the nature of the transition state for protein folding depends predominantly on studies where individual side-chain contributions are mapped out by mutational analysis (phi value analysis). This approach, although extremely powerful, does not in general provide direct information about the...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2007.02.084
更新日期:2007-07-06 00:00:00
abstract::The aim of the present study was to develop the protein fragment complementation assay (PCA) for the intracellular selection of specific binding molecules from the fully synthetic HuCAL antibody library. Here, we describe the first successful selections of specific antibodies by PCA, and we discuss the opportunities a...
journal_title:Journal of molecular biology
pub_type: 杂志文章
doi:10.1016/j.jmb.2005.12.043
更新日期:2006-03-24 00:00:00
abstract::In the "Replicon Theory", Jacob, Brenner and Cuzin proposed the existence of replicators and initiators as the two major actors in DNA replication. Over the years, many protein components of initiators have been shown to be conserved in different organisms during evolution. By contrast, replicator DNA sequences (often...
journal_title:Journal of molecular biology
pub_type: 杂志文章,评审
doi:10.1016/j.jmb.2013.09.023
更新日期:2013-11-29 00:00:00