Abstract:
:The transition between the closed and open conformations of the Sec61 complex permits nascent protein insertion into the translocation channel. A critical event in this structural transition is the opening of the lateral translocon gate that is formed by four transmembrane (TM) spans (TM2, TM3, TM7, and TM8 in Sec61p) to expose the signal sequence-binding site. To gain mechanistic insight into lateral gate opening, mutations were introduced into a lumenal loop (L7) that connects TM7 and TM8. The sec61 L7 mutants were found to have defects in both the posttranslational and cotranslational translocation pathways due to a kinetic delay in channel gating. The translocation defect caused by L7 mutations could be suppressed by the prl class of sec61 alleles, which reduce the fidelity of signal sequence recognition. The prl mutants are proposed to act by destabilizing the closed conformation of the translocation channel. Our results indicate that the equilibrium between the open and closed conformations of the protein translocation channel maintains a balance between translocation activity and signal sequence recognition fidelity.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Trueman SF,Mandon EC,Gilmore Rdoi
10.1091/mbc.E11-01-0070subject
Has Abstractpub_date
2011-09-01 00:00:00pages
2983-93issue
17eissn
1059-1524issn
1939-4586pii
mbc.E11-01-0070journal_volume
22pub_type
杂志文章abstract::Dynamic regulation of cytoskeletal contractility through phosphorylation of the nonmuscle Myosin-II regulatory light chain (MRLC) provides an essential source of tension for shaping epithelial tissues. Rho GTPase and its effector kinase ROCK have been implicated in regulating MRLC phosphorylation in vivo, but evidence...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E10-04-0328
更新日期:2010-08-15 00:00:00
abstract::In Saccharomyces cerevisiae, the class C vacuole protein sorting (Vps) proteins, together with Vam2p/Vps41p and Vam6p/Vps39p, form a complex that interacts with soluble N-ethylmaleimide-sensitive factor attachment protein receptor and Rab proteins to "tether" vacuolar membranes before fusion. To determine a role for t...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-06-0358
更新日期:2004-03-01 00:00:00
abstract::The control of muscle-specific expression is one of the principal mechanisms by which diversity is generated among muscle types. In an attempt to elucidate the regulatory mechanisms that control fiber diversity in any given muscle, we have focused our attention on the transcriptional regulation of the Drosophila Tropo...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-10-0729
更新日期:2004-04-01 00:00:00
abstract::All known mechanisms of mitotic spindle orientation rely on astral microtubules. We report that even in the absence of astral microtubules, metaphase spindles in MDCK and HeLa cells are not randomly positioned along their x-z dimension, but preferentially adopt shallow β angles between spindle pole axis and substratum...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E14-08-1330
更新日期:2015-04-01 00:00:00
abstract::The Drosophila melanogaster genes Hrb87F and Hrb98DE encode the fly proteins HRB87F and HRB98DE (also known as hrp36 and hrp38, respectively) that are most similar in sequence and function to mammalian A/B-type hnRNP proteins. Using overexpression and deletion mutants of Hrb87F, we have tested the hypothesis that the ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.7.7.1059
更新日期:1996-07-01 00:00:00
abstract::The RNA-binding protein HuD binds to a regulatory element in the 3' untranslated region (3' UTR) of the GAP-43 mRNA. To investigate the functional significance of this interaction, we generated PC12 cell lines in which HuD levels were controlled by transfection with either antisense (pDuH) or sense (pcHuD) constructs....
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.9.3191
更新日期:2000-09-01 00:00:00
abstract::Pre-rRNA synthesis and processing are key steps in ribosome biogenesis. Although recent evidence in yeast suggests that these two processes are coupled, the nature of their association is unclear. In this report, we analyze the coordination between rDNA transcription and pre-rRNA processing in mammalian cells. We foun...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e06-03-0249
更新日期:2007-02-01 00:00:00
abstract::Motor neuron (MN) diseases are progressive disorders resulting from degeneration of neuromuscular junctions (NMJs), which form the connection between MNs and muscle fibers. NMJ-in-a-dish models have been developed to examine human MN-associated dysfunction with disease; however such coculture models have randomly orie...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E17-01-0046
更新日期:2017-07-07 00:00:00
abstract::The retinoblastoma (RB) transcriptional corepressor and related family of pocket proteins play central roles in cell cycle control and development, and the regulatory networks governed by these factors are frequently inactivated during tumorigenesis. During normal growth, these proteins are subject to tight control th...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E10-06-0520
更新日期:2010-11-15 00:00:00
abstract::Formins have conserved roles in cell polarity and cytokinesis and directly nucleate actin filament assembly through their FH2 domain. Here, we define the active region of the yeast formin Bni1 FH2 domain and show that it dimerizes. Mutations that disrupt dimerization abolish actin assembly activity, suggesting that di...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-08-0621
更新日期:2004-02-01 00:00:00
abstract::S100A4, a member of the S100 family of Ca(2+)-binding proteins, is directly involved in tumor metastasis. In addition to its expression in tumor cells, S100A4 is expressed in normal cells and tissues, including fibroblasts and cells of the immune system. To examine the contribution of S100A4 to normal physiology, we e...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e09-07-0609
更新日期:2010-08-01 00:00:00
abstract::Zonula occludens (ZO)-1/2/3 are the members of the TJ-MAGUK family of membrane-associated guanylate kinases associated with tight junctions. To investigate the role of ZO-1 (encoded by Tjp1) in vivo, ZO-1 knockout (Tjp1(-/-)) mice were generated by gene targeting. Although heterozygous mice showed normal development a...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e07-12-1215
更新日期:2008-06-01 00:00:00
abstract::Despite the fact that the chromosomal passenger complex is well known to regulate kinetochore behavior in mitosis, no functional link has yet been established between the complex and kinetochore structure. In addition, remarkably little is known about how the complex targets to centromeres. Here, in a study of caspase...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e06-05-0409
更新日期:2007-04-01 00:00:00
abstract::Large cargoes require multiple receptors for efficient transport through the nuclear pore complex. The 60S ribosomal subunit is one of the bulkiest transport cargoes, and in yeast three different receptors, Crm1, Mex67/Mtr2, and Arx1, collaborate in its export. However, only Crm1, recruited by the adapter Nmd3, appear...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-10-1000
更新日期:2009-03-01 00:00:00
abstract::In all orders of life, cell cycle progression in proliferating cells is dependent on cell growth, and the extent of growth required for cell cycle progression is proportional to growth rate. Thus, cells growing rapidly in rich nutrients are substantially larger than slow-growing cells. In budding yeast, a conserved si...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E19-12-0685
更新日期:2020-08-15 00:00:00
abstract::McKusick-Kaufman syndrome (MKKS) is a recessively inherited human genetic disease characterized by several developmental anomalies. Mutations in the MKKS gene also cause Bardet-Biedl syndrome (BBS), a genetically heterogeneous disorder with pleiotropic symptoms. However, little is known about how MKKS mutations lead t...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e07-07-0631
更新日期:2008-03-01 00:00:00
abstract::The function currently attributed to tetraspanins is to organize molecular complexes in the plasma membrane by using multiple cis-interactions. Additionally, the tetraspanin CD9 may be a receptor that binds the soluble ligand PSG17, a member of the immunoglobulin superfamily (IgSF)/CEA subfamily. However, previous dat...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-04-0244
更新日期:2003-12-01 00:00:00
abstract::The architecture of the cytoskeleton and its remodeling are tightly regulated by dynamic reorganization of keratin-rich intermediate filaments. Plakin family proteins associate with the network of intermediate filaments (IFs) and affect its reorganization during migration, differentiation, and response to stress. The ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E18-04-0244
更新日期:2019-02-01 00:00:00
abstract::Keratins are cytoplasmic intermediate filament proteins preferentially expressed by epithelial tissues in a site-specific and differentiation-dependent manner. The complex network of keratin filaments in stratified epithelia is tightly regulated during squamous cell differentiation. Keratin 14 (K14) is expressed in mi...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E10-08-0703
更新日期:2011-11-01 00:00:00
abstract::The formation and maintenance of the bipolar mitotic spindle apparatus require a complex and balanced interplay of several mechanisms, including the stabilization and separation of polar microtubules and the action of various microtubule motors. Nonmicrotubule elements are also present throughout the spindle apparatus...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.3.11.1259
更新日期:1992-11-01 00:00:00
abstract::Damaged DNA-binding protein 2 (DDB2), a nuclear protein, participates in both nucleotide excision repair and mRNA transcription. The transcriptional regulatory function of DDB2 is significant in colon cancer, as it regulates metastasis. To characterize the mechanism by which DDB2 participates in transcription, we inve...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E16-08-0573
更新日期:2017-01-01 00:00:00
abstract::We have shown previously that the Swi5 transcription factor regulates the expression of the SIC1 Cdk inhibitor in late mitosis. This suggests that Swi5 might control other genes with roles in ending mitosis. We identified a gene with a Swi5-binding site in the promoter that encoded a protein with high homology to Pcl2...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.9.4.945
更新日期:1998-04-01 00:00:00
abstract::How recycling receptors are segregated from down-regulated receptors in the endosome is unknown. In previous studies, we demonstrated that substitutions in the transferrin receptor (TR) transmembrane domain (TM) convert the protein from an efficiently recycling receptor to one that is rapidly down regulated. In this s...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.8.2643
更新日期:2000-08-01 00:00:00
abstract::We identified a novel interaction between myosin VI and the GLUT1 transporter binding protein GLUT1CBP(GIPC1) and first proposed that as an adapter molecule it might function to couple vesicle-bound proteins to myosin VI movement. This study refines the model by identifying two myosin VI binding domains in the GIPC1 C...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e04-11-0978
更新日期:2005-09-01 00:00:00
abstract::The conserved NDR-kinase Dbf2 plays a critical role in cytokinesis in budding yeast. Among its cytokinesis-related substrates is the F-BAR protein Hof1. Hof1 colocalizes at the cell division site with the septin complex and, as mitotic exit progresses, moves to the actomyosin ring (AMR). Neither the function of Hof1 a...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E12-08-0608
更新日期:2013-05-01 00:00:00
abstract::A chimeric protein (ERaeq) comprised of the invariant chain (Ii) of class II major histocompatability complex (MHC-II) and aequorin was localized in the endoplasmic reticulum (ER) of transfected human embryonal kidney 293 cells. The targeted aequorin resided in the lumen of the ER membrane system, including the nuclea...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.7.3.419
更新日期:1996-03-01 00:00:00
abstract::Skeletal muscle contains spectrin (or spectrin I) and fodrin (or spectrin II), members of the spectrin supergene family. We used isoform-specific antibodies and cDNA probes to investigate the molecular forms, developmental expression, and subcellular localization of the spectrins in skeletal muscle of the rat. We repo...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.9.1.47
更新日期:1998-01-01 00:00:00
abstract::We describe the development and characterization of a system that allows the rapid and specific induction of individual genes in the yeast Saccharomyces cerevisiae without changes in nutrients or temperature. The system is based on the chimeric transcriptional activator Gal4dbd.ER.VP16 (GEV). Upon addition of the horm...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E11-05-0466
更新日期:2011-11-01 00:00:00
abstract::Vascular integrity and the maintenance of blood vessel continuity are fundamental features of the circulatory system maintained through endothelial cell-cell junctions. Defects in the endothelial barrier become an initiating factor in several pathologies, including ischemia/reperfusion, tumor angiogenesis, pulmonary e...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E13-12-0743
更新日期:2014-07-01 00:00:00
abstract::Signaling via the Ras pathway involves sequential activation of Ras, Raf-1, mitogen-activated protein kinase kinase (MKK), and the extracellular signal-regulated (ERK) group of mitogen-activated protein (MAP) kinases. Expression from the c-Fos, atrial natriuretic factor (ANF), and myosin light chain-2 (MLC-2) promoter...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.6.11.1479
更新日期:1995-11-01 00:00:00