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L1 Protein (l1 + protein)

Distribution by Scientific Domains

Life Sciences	66%
Chemistry	33%

Selected Abstracts

Genetic and clinical aspects of X-linked hydrocephalus (L1 disease): Mutations in the L1CAM gene

HUMAN MUTATION, Issue 1 2001
Sabine Weller
Abstract L1 disease is a group of overlapping clinical phenotypes including X-linked hydrocephalus, MASA syndrome, spastic paraparesis type 1, and X-linked agenesis of corpus callosum. The patients are characterized by hydrocephalus, agenesis or hypoplasia of corpus callosum and corticospinal tracts, mental retardation, spastic paraplegia, and adducted thumbs. The responsible gene, L1CAM, encodes the L1 protein which is a member of the immunoglobulin superfamily of neuronal cell adhesion molecules. The L1 protein is expressed in neurons and Schwann cells and seems to be essential for nervous system development and function. The patients' gene mutations are distributed over the functional protein domains. The exact mechanisms by which these mutations cause a loss of L1 protein function are unknown. There appears to be a relationship between the patients' clinical phenotype and the genotype. Missense mutations in extracellular domains or mutations in cytoplasmic regions cause milder phenotypes than those leading to truncation in extracellular domains or to non-detectable L1 protein. Diagnosis of patients and carriers, including prenatal testing, is based on the characteristic clinical picture and DNA mutation analyses. At present, there is no therapy for the prevention or cure of patients' neurological disabilities. Hum Mutat 18:1,12, 2001. © 2001 Wiley-Liss, Inc. [source]

Stabilization of human papillomavirus virus-like particles by non-ionic surfactants

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2005
Li Shi
Abstract Human papillomavirus (HPV) virus-like-particles (VLPs) produced by recombinant expression systems are promising vaccine candidates for prevention of cervical cancers as well as genital warts. At high protein concentrations, HPV VLPs, comprised of the viral capsid protein L1 and expressed and purified from yeast, are protected against detectable aggregation during preparation and storage by high concentrations of NaCl. At low protein concentrations, however, high salt concentration alone does not fully protect HPV VLPs from aggregation. Moreover, the analytical analysis of HPV VLPs proved to be a challenge due to surface adsorption of HPV VLPs to storage containers and cuvettes. The introduction of non-ionic surfactants into HPV VLP aqueous solutions provides significantly enhanced stabilization of HPV VLPs against aggregation upon exposure to low salt and protein concentration, as well as protection against surface adsorption and aggregation due to heat stress and physical agitation. The mechanism of non-ionic surfactant stabilization of HPV VLPs was extensively studied using polysorbate 80 (PS80) as a representative non-ionic surfactant. The results suggest that PS80 stabilizes HPV VLPs mainly by competing with the VLPs for various container surfaces and air/water interfaces. No appreciable binding of PS80 to intact HPV VLPs was observed although PS80 does bind to the denatured HPV L1 protein. Even in the presence of stabilizing level of PS80, however, an ionic strength dependence of HPV VLP stabilization against aggregation is observed indicating optimization of both salt and non-ionic surfactant levels is required for effective stabilization of HPV VLPs in solution. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:1538,1551, 2005 [source]

Human papillomavirus L1 protein expressed in tobacco chloroplasts self-assembles into virus-like particles that are highly immunogenic

PLANT BIOTECHNOLOGY JOURNAL, Issue 5 2008
Alicia Fernández-San Millán
Summary Cervical cancer is the second most prevalent cancer in women worldwide. It is linked to infection with human papillomavirus (HPV). As the virus cannot be propagated in culture, vaccines based on virus-like particles have been developed and recently marketed. However, their high costs constitute an important drawback for widespread use in developing countries, where the incidence of cervical cancer is highest. In a search for alternative production systems, the major structural protein of the HPV-16 capsid, L1, was expressed in tobacco chloroplasts. A very high yield of production was achieved in mature plants (~3 mg L1/g fresh weight; equivalent to 24% of total soluble protein). This is the highest expression level of HPV L1 protein reported in plants. A single mature plant synthesized ~240 mg of L1. The chloroplast-derived L1 protein displayed conformation-specific epitopes and assembled into virus-like particles, visible by transmission electron microscopy. Furthermore, leaf protein extracts from L1 transgenic plants were highly immunogenic in mice after intraperitoneal injection, and neutralizing antibodies were detected. Taken together, these results predict a promising future for the development of a plant-based vaccine against HPV. [source]

Role of the cytoplasmic domain of the L1 cell adhesion molecule in brain development

THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 7 2010
Yukiko Nakamura
Abstract Mutations in the human L1CAM gene cause X-linked hydrocephalus and MASA (Mental retardation, Aphasia, Shuffling gait, Adducted thumbs) syndrome. In vitro studies have shown that the L1 cytoplasmic domain (L1CD) is involved in L1 trafficking, neurite branching, signaling, and interactions with the cytoskeleton. L1cam knockout (L1KO) mice have hydrocephalus, a small cerebellum, hyperfasciculation of corticothalamic tracts, and abnormal peripheral nerves. To explore the function of the L1CD, we made three new mice lines in which different parts of the L1CD have been altered. In all mutant lines L1 protein is expressed and transported into the axon. Interestingly, these new L1CD mutant lines display normal brain morphology. However, the expression of L1 protein in the adult is dramatically reduced in the two L1CD mutant lines that lack the ankyrin-binding region and they show defects in motor function. Therefore, the L1CD is not responsible for the major defects observed in L1KO mice, yet it is required for continued L1 protein expression and motor function in the adult. J. Comp. Neurol. 518:1113,1132, 2010. © 2009 Wiley-Liss, Inc. [source]

Ribosome motions modulate electrostatic properties

BIOPOLYMERS, Issue 6 2004
Joanna Trylska
Abstract The electrostatic properties of the 70S ribosome of Thermus thermophilus were studied qualitatively by solving the Poisson,Boltzmann (PB) equation in aqueous solution and with physiological ionic strength. The electrostatic potential was calculated for conformations of the ribosome derived by recent normal mode analysis (Tama, F., et al. Proc Natl Acad Sci USA 2003 100, 9319,9323) of the ratchet-like reorganization that occurs during translocation (Frank, J.; Agrawal, R. K. Nature 2000 406, 318,322). To solve the PB equation, effective parameters (charges and radii), applicable to a highly charged backbone model of the ribosome, were developed. Regions of positive potential were found at the binding site of the elongation factors G and Tu, as well as where the release factors bind. Large positive potential areas are especially pronounced around the L11 and L6 proteins. The region around the L1 protein is also positively charged, supporting the idea that L1 may interact with the E-site tRNA during its release from the ribosome after translocation. Functional rearrangement of the ribosome leads to electrostatic changes which may help the translocation of the tRNAs during the elongation stage. © 2004 Wiley Periodicals, Inc. Biopolymers, 2004 [source]

Structure of ribosomal protein L1 from Methanococcus thermolithotrophicus.

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 6-2 2002
Functionally important structural invariants on the L1 surface
The crystal structure of ribosomal protein L1 from the archaeon Methanococcus thermolithotrophicus has been determined at 2.7,Å resolution. The crystals belong to space group P212121, with unit-cell parameters a = 67.0, b = 70.1, c = 106.3,Å and two molecules per asymmetric unit. The structure was solved by the molecular-replacement method with AMoRe and refined with CNS to an R value of 18.9% and an Rfree of 25.4% in the resolution range 30,2.7,Å. Comparison of this structure with those obtained previously for two L1 proteins from other sources (the bacterium Thermus thermophilus and the archaeon M. jannaschii) as well as detailed analysis of intermolecular contacts in the corresponding L1 crystals reveal structural invariants on the molecular surface which are probably important for binding the 23S ribosomal RNA and protein function within the ribosome. [source]