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121.
Eberhard Warkentin Sina Weidenweber Karola Schühle Ulrike Demmer Johann Heider Ulrich Ermler 《Proteins》2017,85(11):2017-2023
Common structural elements in proteins such as α‐helices or β‐sheets are characterized by uniformly repeating, energetically favorable main chain conformations which additionally exhibit a completely saturated hydrogen‐bonding network of the main chain NH and CO groups. Although polyproline or polyglycine type II helices (PPII or PGII) are frequently found in proteins, they are not considered as equivalent secondary structure elements because they do not form a similar self‐contained hydrogen‐bonding network of the main chain atoms. In this context our finding of an unusual motif of glycine‐rich PGII‐like helices in the structure of the acetophenone carboxylase core complex is of relevance. These PGII‐like helices form hexagonal bundles which appear to fulfill the criterion of a (largely) saturated hydrogen‐bonding network of the main‐chain groups and therefore may be regarded in this sense as a new secondary structure element. It consists of a central PGII‐like helix surrounded by six nearly parallel PGII‐like helices in a hexagonal array, plus an additional PGII‐like helix extending the array outwards. Very related structural elements have previously been found in synthetic polyglycine fibers. In both cases, all main chain NH and CO groups of the central PGII‐helix are saturated by either intra‐ or intermolecular hydrogen‐bonds, resulting in a self‐contained hydrogen‐bonding network. Similar, but incomplete PGII‐helix patterns were also previously identified in a GTP‐binding protein and an antifreeze protein. 相似文献
122.
Ylisaukko-oja T Rehnström K Vanhala R Tengström C Lähdetie J Järvelä I 《Human genetics》2004,114(2):211-213
Mutations in the coding region of the angiotensin II type 2 receptor gene (AGTR2) were recently identified to cause X-linked recessive mental retardation. We report a mutation screening of the AGTR2 gene in 57 Finnish male patients with non-syndromic mental retardation. We identified two mutations, a 62GT transversion, which leads to a substitution of glycine for valine (G21V) and a 157AT transversion, which causes a substitution of isoleucine for phenylalanine (I53F). The patients with AGTR2 sequence variants had severe/profound mental retardation, epileptic seizures, restlessness, hyperactivity, and disturbed development of speech. 相似文献
123.
Jakub Jez Alexandra Castilho Josephine Grass Karola Vorauer-Uhl Thomas Sterovsky Friedrich Altmann Prof. Herta Steinkellner 《Biotechnology journal》2013,8(3):371-382
Recombinant human erythropoietin (rhEPO), a glycohormone, is one of the leading biopharmaceutical products. The production of rhEPO is currently restricted to mammalian cell expression systems because of rhEPO's highly complex glycosylation pattern, which is a major determinant for drug-efficacy. Here we evaluate the ability of plants to produce different glycoforms of rhEPO. cDNA constructs were delivered to Nicotiana benthamiana (N. benthamiana) and transiently expressed by a viral based expression system. Expression levels up to 85 mg rhEPO/kg fresh leaf material were achieved. Moreover, co-expression of rhEPO with six mammalian genes required for in planta protein sialylation resulted in the synthesis of rhEPO decorated mainly with bisialylated N-glycans (NaNa), the most abundant glycoform of circulating hEPO in patients with anemia. A newly established peptide tag (ELDKWA) fused to hEPO was particularly well-suited for purification of the recombinant hormone based on immunoaffinity. Subsequent lectin chromatography allowed enrichment of exclusively sialylated rhEPO. All plant-derived glycoforms exhibited high biological activity as determined by a cell-based receptor-binding assay. The generation of rhEPO carrying largely homogeneous glycosylation profiles (GnGnXF, GnGn, and NaNa) will facilitate further investigation of functionalities with potential implications for medical applications. 相似文献
124.
The broadly neutralizing anti-HIV-1 2F5 monoclonal antibody recognizes a gp41 epitope proximal to the viral membrane. Potential phospholipid autoreactivity at cell surfaces has raised concerns about the use of this antibody for development of vaccines or immunotherapy. In this study, confocal microscopy of giant unilamellar vesicles (GUVs) was used to assess 2F5 reactivity with phospholipids assembled into bilayers with surface charge and curvature stress approximating those of the eukaryotic plasma membranes. Antibody partitioning into lipid bilayers required the specific recognition of membrane-inserted epitope, indicating that 2F5 was unable to directly react with GUV phospholipids, even under fluid phase segregation conditions. Our results thus support the feasibility of raising 2F5-like neutralizing responses through vaccination, and the medical safety of mAb infusions. 相似文献