scholarly journals Visualizing key hinges and a potential major source of compliance in the lever arm of myosin

2010 ◽  
Vol 108 (1) ◽  
pp. 114-119 ◽  
Author(s):  
Jerry H. Brown ◽  
V. S. Senthil Kumar ◽  
Elizabeth O’Neall-Hennessey ◽  
Ludmila Reshetnikova ◽  
Howard Robinson ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Heavy Chain ◽  
Light Chain ◽  
Potential Role ◽  
Phosphorylation Site ◽  
Alpha Helix ◽  
Localized Source ◽  
Lever Arm ◽  
Sea Scallop ◽  
Relative Proximity

We have determined the 2.3-Å-resolution crystal structure of a myosin light chain domain, corresponding to one type found in sea scallop catch (“smooth”) muscle. This structure reveals hinges that may function in the “on” and “off” states of myosin. The molecule adopts two different conformations about the heavy chain “hook” and regulatory light chain (RLC) helix D. This conformational change results in extended and compressed forms of the lever arm whose lengths differ by 10 Å. The heavy chain hook and RLC helix D hinges could thus serve as a potential major and localized source of cross-bridge compliance during the contractile cycle. In addition, in one of the molecules of the crystal, part of the RLC N-terminal extension is seen in atomic detail and forms a one-turn alpha-helix that interacts with RLC helix D. This extension, whose sequence is highly variable in different myosins, may thus modulate the flexibility of the lever arm. Moreover, the relative proximity of the phosphorylation site to the helix D hinge suggests a potential role for conformational changes about this hinge in the transition between the on and off states of regulated myosins.

LIPOPOLYSACCHARIDE-SENSITIVE SERINE-PROTEASE ZYMOGEN (FACTOR C) OF LIMULUS HEMOCYTES: IDENTIFICATION AND ALIGNMENT OF PROTEOLYTIC FRAGMENTS PRODUCED DURING THE ACTIVATION SHOW THAT IT IS A NOVEL TYPE OF SERINE-PROTEASE

1987 ◽  
Author(s):  
F Tokunaga ◽  
T Miyata ◽  
T Nakamura ◽  
T Morita ◽  
S Iwanaga
Keyword(s):  
Serine Protease ◽  
Heavy Chain ◽  
Light Chain ◽  
Interleukin 2 ◽  
Coagulation Factor ◽  
Clotting Factor ◽  
Single Chain ◽  
Terminal Sequence ◽  
A Chain ◽  
Factor C

Limulus clotting factor, factor C, is a lipopolysaccharide (LPS)-sensitive serine-protease zymogen present in the hemocytes. It is a two-chain glycoprotein (M.W. = 123,000) composed of a heavy chain (M.W. = 80,000) and a light chain (M.W. = 43,000) T. Nakamura et al. (1986) Eur. J. Biochem. 154, 511-521 .On further studies of this zymogen, a single-chain factor C (M.W. = 123,000) was identified by Western blotting technique. The heavy chain had an NH2-terminal sequence of Ser-Gly-Val-Asp-, which was consistent with the NH2-terminal sequence of the single-chain factor C, indicating that the heavy chain is located in the NH2-terminal part of the zymogen. The light chain had an NH22-terminal sequence of Ser-Ser-Gln-Pro-. Incubation of the two-chain zymogen with LPS resulted in the cleavage of a Phe-Ile bond between residues 72 and 73 of the light chain. Concomitant with this cleavage, the A (72.amino acids) and B chains derived from the light chain was formed. The complete amino acid sequence of the A chain was determined by automated Edman degradation. The A chain contained a typical segment which is similar structuraly to those a family of repeats in human β2 -glycoprotein I, complement factors B, Clr, Cls, H, C4b-binding protein, 02, coagulation factor XIII b subunit, haptoglobin a chain, and interleukin 2 receptor. The NH2-terminal sequence of the B chain was Ile-Trp-Asn-Gly-. This chain contained the serine-active site sequence of -ASP-Ala-Cys-Ser-Gly-Asp-SER-Gly-Gly-Pro-.These results indicate that limulus factor C exists in the hemocytes in a single-chain zymogen form and is converted to an active serine-protease by hydrolysis of a specific Phe-Ile peptide bond. The correlation of limulus factor C and mammalian complement proteins was also suggested.

scholarly journals EGFR-ERK induced activation of GRHL1 promotes cell cycle progression by up-regulating cell cycle related genes in lung cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Yiming He ◽  
Mingxi Gan ◽  
Yanan Wang ◽  
Tong Huang ◽  
Jianbin Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Potential Role ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Phosphorylation Site ◽  
Promoter Regions ◽  
Cycle Progression

AbstractGrainyhead-like 1 (GRHL1) is a transcription factor involved in embryonic development. However, little is known about the biological functions of GRHL1 in cancer. In this study, we found that GRHL1 was upregulated in non-small cell lung cancer (NSCLC) and correlated with poor survival of patients. GRHL1 overexpression promoted the proliferation of NSCLC cells and knocking down GRHL1 inhibited the proliferation. RNA sequencing showed that a series of cell cycle-related genes were altered when knocking down GRHL1. We further demonstrated that GRHL1 could regulate the expression of cell cycle-related genes by binding to the promoter regions and increasing the transcription of the target genes. Besides, we also found that EGF stimulation could activate GRHL1 and promoted its nuclear translocation. We identified the key phosphorylation site at Ser76 on GRHL1 that is regulated by the EGFR-ERK axis. Taken together, these findings elucidate a new function of GRHL1 on regulating the cell cycle progression and point out the potential role of GRHL1 as a drug target in NSCLC.

scholarly journals Variance analysis of immunoglobulin alleles in natural populations of rabbit (Oryctolagus cuniculus): the extensive interallelic divergence at the b locus could be the outcome of overdominance-type selection.

Genetics ◽  
1993 ◽  
Vol 135 (1) ◽  
pp. 171-187 ◽  
Author(s):  
W van der Loo
Keyword(s):  
Heavy Chain ◽  
Light Chain ◽  
Gene Diversity ◽  
Natural Populations ◽  
Constant Region ◽  
Immunoglobulin Light Chain ◽  
Evolutionary Patterns ◽  
B Locus ◽  
Type Selection ◽  
Predominant Allele

Abstract Population genetic data are presented which should contribute to evaluation of the hypothesis that the extraordinary evolutionary patterns observed at the b locus of the rabbit immunoglobulin light chain constant region can be the outcome of overdominance-type selection. The analysis of allele correlations in natural populations revealed an excess of heterozygotes of about 10% at the b locus while heterozygote excess was not observed at loci determining the immunoglobulin heavy chain. Data from the published literature, where homozygote advantage was suggested, were reevaluated and found in agreement with data here presented. Gene diversity was evenly distributed among populations and showed similarities with patterns reported for histocompatibility loci. Analysis of genotypic disequilibria revealed strong digenic associations between the leading alleles of heavy and light chain constant region loci in conjunction with trigenic disequilibria corresponding to a preferential association of b locus heterozygosity with the predominant allele of the heavy chain e locus. It is argued that this may indicate compensatory or nonadditive aspects of a putative heterozygosity enhancing mechanism, implying that effects at the light chain might be more pronounced in populations fixed for the heavy chain polymorphism.

scholarly journals Critical roles of the immunoglobulin intronic enhancers in maintaining the sequential rearrangement of IgH and Igk loci

2006 ◽  
Vol 203 (7) ◽  
pp. 1721-1732 ◽  
Author(s):  
Matthew A. Inlay ◽  
Tongxiang Lin ◽  
Heather H. Gao ◽  
Yang Xu
Keyword(s):  
B Cells ◽  
Developmental Stage ◽  
Heavy Chain ◽  
Light Chain ◽  
Matrix Attachment Region ◽  
Cis Elements ◽  
Wild Type ◽  
Intronic Enhancer ◽  
Attachment Region

V(D)J recombination of immunoglobulin (Ig) heavy (IgH) and light chain genes occurs sequentially in the pro– and pre–B cells. To identify cis-elements that dictate this order of rearrangement, we replaced the endogenous matrix attachment region/Igk intronic enhancer (MiEκ) with its heavy chain counterpart (Eμ) in mice. This replacement, denoted EμR, substantially increases the accessibility of both Vκ and Jκ loci to V(D)J recombinase in pro–B cells and induces Igk rearrangement in these cells. However, EμR does not support Igk rearrangement in pre–B cells. Similar to that in MiEκ−/− pre–B cells, the accessibility of Vκ segments to V(D)J recombinase is considerably reduced in EμR pre–B cells when compared with wild-type pre–B cells. Therefore, Eμ and MiEκ play developmental stage-specific roles in maintaining the sequential rearrangement of IgH and Igk loci by promoting the accessibility of V, D, and J loci to the V(D)J recombinase.

scholarly journals Regulatory Light Chain Mutants Linked to Heart Disease Modify the Cardiac Myosin Lever Arm

Biochemistry ◽  
2013 ◽  
Vol 52 (7) ◽  
pp. 1249-1259 ◽  
Author(s):  
Thomas P. Burghardt ◽  
Laura A. Sikkink
Keyword(s):  
Heart Disease ◽  
Light Chain ◽  
Regulatory Light Chain ◽  
Cardiac Myosin ◽  
Lever Arm
Sign in / Sign up

Export Citation Format

Share Document