A point mutation in the regulatory light chain reduces the step size of skeletal muscle myosin.

Abstract:

:Current evidence favors the theory that, when the globular motor domain of myosin attaches to actin, the light chain binding domain or "lever arm" rotates, and thereby generates movement of actin filaments. Myosin is uniquely designed for such a role in that a long alpha-helix (approximately 9 nm) extending from the C terminus of the catalytic core is stabilized by two calmodulin-like molecules, the regulatory light chain (RLC) and the essential light chain (ELC). Here, we introduce a single-point mutation into the skeletal myosin RLC, which results in a large (approximately 50%) reduction in actin filament velocity (V(actin)) without any loss in actin-activated MgATPase activity. Single-molecule analysis of myosin by optical trapping showed a comparable 2-fold reduction in unitary displacement or step size (d), without a significant change in the duration of the strongly attached state (tau(on)) after the power stroke. Assuming that V(actin) approximately d/tau(on), we can account for the change in velocity primarily by a change in the step size of the lever arm without incurring any change in the kinetic properties of the mutant myosin. These results suggest that a principal role for the many light chain isoforms in the myosin II class may be to modulate the flexural rigidity of the light chain binding domain to maximize tension development and movement during muscle contraction.

authors

Sherwood JJ,Waller GS,Warshaw DM,Lowey S

doi

10.1073/pnas.0401699101

keywords:

subject

Has Abstract

pub_date

2004-07-27 00:00:00

pages

10973-8

issue

30

eissn

0027-8424

issn

1091-6490

pii

0401699101

journal_volume

101

pub_type

杂志文章
  • The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds.

    abstract::Berninamycin is a member of the pyridine-containing thiopeptide class of antibiotics that undergoes massive posttranslational modifications from ribosomally generated preproteins. Berninamycin has a 2-oxazolyl-3-thiazolyl-pyridine core embedded in a 35-atom macrocycle rather than typical trithiazolylpyridine cores emb...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1307111110

    authors: Malcolmson SJ,Young TS,Ruby JG,Skewes-Cox P,Walsh CT

    更新日期:2013-05-21 00:00:00

  • Structure of a paramyxovirus polymerase complex reveals a unique methyltransferase-CTD conformation.

    abstract::Paramyxoviruses are enveloped, nonsegmented, negative-strand RNA viruses that cause a wide spectrum of human and animal diseases. The viral genome, packaged by the nucleoprotein (N), serves as a template for the polymerase complex, composed of the large protein (L) and the homo-tetrameric phosphoprotein (P). The ∼250-...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1919837117

    authors: Abdella R,Aggarwal M,Okura T,Lamb RA,He Y

    更新日期:2020-03-03 00:00:00

  • Significant liquid-structure theory of viscosity and self-diffusion of the alkali metals.

    abstract::Significant liquid-structure theory has been used to calculate the transport properties of the alkali metals. Unlike previous calculations, the volume and temperature dependence of the solid-like structure has been taken into consideration. Equations for the potential energy as a function of volume of the alkali metal...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.6.1342

    authors: Hsu CC,Eyring H

    更新日期:1972-06-01 00:00:00

  • Amorphous diamond-structured photonic crystal in the feather barbs of the scarlet macaw.

    abstract::Noniridescent coloration by the spongy keratin in parrot feather barbs has fascinated scientists. Nonetheless, its ultimate origin remains as yet unanswered, and a quantitative structural and optical description is still lacking. Here we report on structural and optical characterizations and numerical simulations of t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1204383109

    authors: Yin H,Dong B,Liu X,Zhan T,Shi L,Zi J,Yablonovitch E

    更新日期:2012-07-03 00:00:00

  • Metric rigidity theorems on Hermitian locally symmetric spaces.

    abstract::Let X = Omega/Gamma be a compact quotient of an irreducible bounded symmetric domain Omega of rank >/=2 by a discrete group omega of automorphisms without fixed points. It is well known that the Kähler-Einstein metric g on X carries seminegative curvature (in the sense of Griffiths). I show that any Hermitian metric h...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.8.2288

    authors: Mok N

    更新日期:1986-04-01 00:00:00

  • A biochemical approach to identifying microRNA targets.

    abstract::Identifying the downstream targets of microRNAs (miRNAs) is essential to understanding cellular regulatory networks. We devised a direct biochemical method for miRNA target discovery that combined RNA-induced silencing complex (RISC) purification with microarray analysis of bound mRNAs. Because targets of miR-124a hav...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0709971104

    authors: Karginov FV,Conaco C,Xuan Z,Schmidt BH,Parker JS,Mandel G,Hannon GJ

    更新日期:2007-12-04 00:00:00

  • Parallel processing of serial movements in prefrontal cortex.

    abstract::A key idea in Lashley's formulation of the problem of serial order in behavior is the postulated neural representation of all serial elements before the action begins. We studied this question by recording the activity of individual neurons simultaneously in small ensembles in prefrontal cortex while monkeys copied ge...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.162485599

    authors: Averbeck BB,Chafee MV,Crowe DA,Georgopoulos AP

    更新日期:2002-10-01 00:00:00

  • Optical imaging of the spatial distribution of beta-particles emerging from surfaces.

    abstract::The multiplication in gases of ionization electrons, by the effect of the electric fields between parallel electrodes, leads to the emission of light from the molecules excited in the avalanche process. The optical imaging of this light, with intensifiers, on charge-coupled devices permits the localization, in the gas...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.6.1741

    authors: Charpak G,Dominik W,Zaganidis N

    更新日期:1989-03-01 00:00:00

  • Coordinate occupancy of AP-1 sites in the vitamin D-responsive and CCAAT box elements by Fos-Jun in the osteocalcin gene: model for phenotype suppression of transcription.

    abstract::Osteocalcin, a bone-specific protein and marker of the mature osteoblast, is expressed only in nonproliferating osteoblasts in a mineralizing extracellular matrix, while type I collagen is expressed in proliferating cells. The nuclear proteins encoded by the c-fos and c-jun protooncogenes are expressed during the prol...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.24.9990

    authors: Owen TA,Bortell R,Yocum SA,Smock SL,Zhang M,Abate C,Shalhoub V,Aronin N,Wright KL,van Wijnen AJ

    更新日期:1990-12-01 00:00:00

  • Gene-based vaccines and immunotherapeutics.

    abstract::DNA vaccines, comprised of plasmid DNA encoding proteins from pathogens, allergens, and tumors, are being evaluated as prophylactic vaccines and therapeutic treatments for infectious diseases, allergies, and cancer; plasmids encoding normal human proteins are likewise being tested as vaccines and treatments for autoim...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.0404845101

    authors: Liu M,Acres B,Balloul JM,Bizouarne N,Paul S,Slos P,Squiban P

    更新日期:2004-10-05 00:00:00

  • Transfer of the human gene for hypoxanthine-guanine phosphoribosyltransferase via isolated human metaphase chromosomes into mouse L-cells.

    abstract::We have transferred the human gene for hypoxanthine-guanine phosphoribosyltransferase (HPRT, EC 2.4.2.8; IMP:pyrophosphate phosphoribosyltransferease) via isolated metaphase chromosomes from human HeLa S3 cells into murine A9 cells which lack functional murine HPRT activity, using the technique of McBride and Ozer (Pr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.5.1792

    authors: Willecke K,Ruddle FH

    更新日期:1975-05-01 00:00:00

  • Mammalian Golgi apparatus UDP-N-acetylglucosamine transporter: molecular cloning by phenotypic correction of a yeast mutant.

    abstract::Transporters in the Golgi apparatus membrane translocate nucleotide sugars from the cytosol into the Golgi lumen before these can be substrates for the glycosylation of proteins, lipids, and proteoglycans. We have cloned the mammalian Golgi membrane transporter for uridine diphosphate-N-acetylglucosamine by phenotypic...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.14.7888

    authors: Guillen E,Abeijon C,Hirschberg CB

    更新日期:1998-07-07 00:00:00

  • Regulation of T-cell antigen receptor (TCR) alpha-chain expression by TCR beta-chain transcripts.

    abstract::The TCR is an alpha beta heterodimer, a part of the multimeric structure through which physiological T-cell activation occurs. The expression of TCR alpha chain is greatly diminished in a beta-chain-deficient mutant Jurkat cell line (J.RT3-T3.5). The relationship between the expression of the TCR alpha and beta chains...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.9.3712

    authors: Chung S,Strominger JL

    更新日期:1995-04-25 00:00:00

  • Enhanced recombination between lambda plac5 and F42lac: identification of cis- and trans-acting factors.

    abstract::Enhanced transductional recombination between specialized transducing phage lambda plac5 and plasmid F42lac depends on cis- and trans-acting factors. By constructing a series of recombinant molecules, the cis-acting site required for enhanced recombination has been identified as oriT, the origin of conjugational trans...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.23.7500

    authors: Seifert HS,Porter RD

    更新日期:1984-12-01 00:00:00

  • Eukaryotic Mr 83,000 heat shock protein has a homologue in Escherichia coli.

    abstract::We have isolated a gene from Escherichia coli homologous to the gene encoding the Mr 83,000 Drosophila heat shock protein (hsp83). In E. coli the protein homologous to hsp83 is a heat shock protein called C62.5. The predicted amino acid sequence of C62.5 is 41% and 42% identical to the Drosophila and human hsp83 prote...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.15.5177

    authors: Bardwell JC,Craig EA

    更新日期:1987-08-01 00:00:00

  • The amphisbaenian ear: Blanus cinereus and Diplometopon zarudnyi.

    abstract::Observations on the structure and function of the ear in amphisbaenians have been extended to two new species: to Blanus cinereus of the family Amphisbaenidae and Diplometopon zarudnyi of the family Trogonophidae. Blanus, considered one of the most primitive of this group of reptiles, shows a distinctive form of sound...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.4.1487

    authors: Gans C,Wever EG

    更新日期:1975-04-01 00:00:00

  • Construction and properties of Tn917-lac, a transposon derivative that mediates transcriptional gene fusions in Bacillus subtilis.

    abstract::A derivative of Tn917 was constructed, referred to as Tn917-lac, which is capable of generating fusions that connect the transcripts of Bacillus subtilis chromosomal genes to the coding sequence of the lacZ gene of Escherichia coli. Two independent insertions of Tn917-lac into the gltA gene and one insertion into the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.1.140

    authors: Perkins JB,Youngman PJ

    更新日期:1986-01-01 00:00:00

  • Target neuron-specific process formation by embryonic mesencephalic dopamine neurons in vitro.

    abstract::Mesencephalic dopamine neurons from the embryonic mouse brain were dissociated, aggregated in vitro in the presence of dissociated cells from appropriate or inappropriate target neuron areas, and visualized by the Falck-Hillarp histofluorescence technique after exposure to 1 microM exogenous dopamine. When aggregated ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.2.1264

    authors: Hemmendinger LM,Garber BB,Hoffmann PC,Heller A

    更新日期:1981-02-01 00:00:00

  • The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: a clue for a role of NOVH in cell-adhesion signaling.

    abstract::The NOVH protein belongs to the emerging CCN [Connective tissue growth factor (CTGF), Cyr61/Cef10, nephroblastoma overexpressed gene] family of growth regulators sharing a strikingly conserved multimodular organization but exhibiting distinctive functional features. Two members of the family (CYR61 and CTGF) are posit...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.3.869

    authors: Perbal B,Martinerie C,Sainson R,Werner M,He B,Roizman B

    更新日期:1999-02-02 00:00:00

  • The timing of phasic transmitter release is Ca2+-dependent and lacks a direct influence of presynaptic membrane potential.

    abstract::Ca2+ influx through voltage-gated Ca2+ channels and the resulting elevation of intracellular Ca2+ concentration, [Ca2+]i, triggers transmitter release in nerve terminals. However, it is controversial whether in addition to the opening of Ca2+ channels, membrane potential directly affects transmitter release. Here, we ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2433276100

    authors: Felmy F,Neher E,Schneggenburger R

    更新日期:2003-12-09 00:00:00

  • Synthesis of (-)-longithorone A: using organic synthesis to probe a proposed biosynthesis.

    abstract::We present a full report of our enantioselective synthesis of (-)-longithorone A (1). The synthesis was designed to test the feasibility of the biosynthetic proposal for 1 put forward by Schmitz involving intermolecular and transannular Diels-Alder reactions of two [12]-paracyclophane quinones. We have found that if t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0401952101

    authors: Morales CA,Layton ME,Shair MD

    更新日期:2004-08-17 00:00:00

  • Colloquium paper: terrestrial apes and phylogenetic trees.

    abstract::The image that best expresses Darwin's thinking is the tree of life. However, Darwin's human evolutionary tree lacked almost everything because only the Neanderthals were known at the time and they were considered one extreme expression of our own species. Darwin believed that the root of the human tree was very deep ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0914614107

    authors: Arsuaga JL

    更新日期:2010-05-11 00:00:00

  • Myelin sheath structure and regeneration in peripheral nerve injury repair.

    abstract::Observing the structure and regeneration of the myelin sheath in peripheral nerves following injury and during repair would help in understanding the pathogenesis and treatment of neurological diseases caused by an abnormal myelin sheath. In the present study, transmission electron microscopy, immunofluorescence stain...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1910292116

    authors: Liu B,Xin W,Tan JR,Zhu RP,Li T,Wang D,Kan SS,Xiong DK,Li HH,Zhang MM,Sun HH,Wagstaff W,Zhou C,Wang ZJ,Zhang YG,He TC

    更新日期:2019-10-29 00:00:00

  • Targeted gene walking by low stringency polymerase chain reaction: assignment of a putative human brain sodium channel gene (SCN3A) to chromosome 2q24-31.

    abstract::We have developed a low stringency polymerase chain reaction (LSPCR) to isolate the unknown neighboring region around a known DNA sequence, thus allowing efficient targeted gene walking. The method involves the polymerase chain reaction (PCR) with a single primer under conditions of low stringency for primer annealing...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.8.2975

    authors: Malo MS,Srivastava K,Andresen JM,Chen XN,Korenberg JR,Ingram VM

    更新日期:1994-04-12 00:00:00

  • Biological function of gramicidin: studies on gramicidin-negative mutants.

    abstract::By the use of a rapid radioautographic screening procedure, two mutants of Bacillus brevis ATCC 8185 that have lost the ability to produce gramicidin have been isolated. These mutants produced normal levels of tyrocidine and sporulated at the same frequency as the parent strain. Their spores, however, were more heat-s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.74.2.780

    authors: Mukherjee PK,Paulus H

    更新日期:1977-02-01 00:00:00

  • Selective association of misfolded ALS-linked mutant SOD1 with the cytoplasmic face of mitochondria.

    abstract::Mutations in copper/zinc superoxide dismutase (SOD1) are causative for dominantly inherited amyotrophic lateral sclerosis (ALS). Despite high variability in biochemical properties among the disease-causing mutants, a proportion of both dismutase-active and -inactive mutants are stably bound to spinal cord mitochondria...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0712209105

    authors: Vande Velde C,Miller TM,Cashman NR,Cleveland DW

    更新日期:2008-03-11 00:00:00

  • Similar DNA recognition properties of alternatively spliced Drosophila POU factors.

    abstract::The POU-IV or "Brn-3" class of POU-domain transcription factors is represented in Drosophila by I-POU and twin-of-I-POU, alternative splice products of the I-POU gene. I-POU has been previously reported to inhibit DNA binding by the POU-III class factor drifter/Cf1a via the formation of heterodimeric complexes. Here w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.26.15097

    authors: Turner EE

    更新日期:1996-12-24 00:00:00

  • Systemic anti-VEGF treatment strongly reduces skin inflammation in a mouse model of psoriasis.

    abstract::Although(,) vascular remodeling is a hallmark of many chronic inflammatory disorders such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis, anti-vascular strategies to treat these conditions have received little attention to date. We investigated the anti-inflammatory activity of systemic blockade of...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0907550106

    authors: Schonthaler HB,Huggenberger R,Wculek SK,Detmar M,Wagner EF

    更新日期:2009-12-15 00:00:00

  • An estrogen-dependent four-gene micronet regulating social recognition: a study with oxytocin and estrogen receptor-alpha and -beta knockout mice.

    abstract::Estrogens control many physiological and behavioral processes, some of which are connected to reproduction. These include sexual and other social behaviors. Here we implicate four gene products in a micronet required for mammalian social recognition, through which an individual learns to recognize other individuals. F...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0631699100

    authors: Choleris E,Gustafsson JA,Korach KS,Muglia LJ,Pfaff DW,Ogawa S

    更新日期:2003-05-13 00:00:00

  • Regeneration of a functional RNA virus genome by recombination between deletion mutants and requirement for cowpea chlorotic mottle virus 3a and coat genes for systemic infection.

    abstract::RNAs 1 and 2 of the tripartite cowpea chlorotic mottle virus (CCMV) genome are sufficient for RNA replication in protoplasts, whereas systemic infection of cowpea plants additionally requires RNA3, which encodes the 3a noncapsid protein and coat protein. By using biologically active CCMV cDNA clones, we find that dele...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.5.1820

    authors: Allison R,Thompson C,Ahlquist P

    更新日期:1990-03-01 00:00:00