New α2 globin chain variant with low oxygen affinity affecting the N‐terminal residue and leading to N‐acetylation [Hb Lyon‐Bron α 1(NA1)Val→Ac‐Ala]

Lacan, Philippe; Souillet, G; Aubry, Marc; Promé, Danièlle; Richelme‐David, Suzy; Kister, J.; Wajcman, Henri; Francina, Alain

doi:10.1002/ajh.10051

Cited by 13 publications

(2 citation statements)

References 17 publications

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“…Acetylation of the native protein, but not the recombinant one, may also contribute to the observed functional differences. Indeed Lacan et al (54) showed that a new ␣-chain variant, Hb LyonByron, is characterized by the replacement of the N-terminal valine by an alanine that is N-terminal acetylated. This resulted in a decreased oxygen affinity.…”

Section: Resultsmentioning

confidence: 99%

The Nerve Hemoglobin of the Bivalve Mollusc Spisula solidissima

Dewilde

Ebner

Vinck

et al. 2006

Journal of Biological Chemistry

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Members of the hemoglobin (Hb) superfamily are present in nerve tissue of several vertebrate and invertebrate species. In vertebrates they display hexacoordinate heme iron atoms and are typically expressed at low levels (M). Their function is still a matter of debate. In invertebrates they have a hexa-or pentacoordinate heme iron, are mostly expressed at high levels (mM), and have been suggested to have a myoglobin-like function. The native Hb of the surf clam, Spisula solidissima, composed of 162 amino acids, does not show specific deviations from the globin templates. UV-visible and resonance Raman spectroscopy demonstrate a hexacoordinate heme iron. Based on the sequence analogy, the histidine E7 is proposed as a sixth ligand. Kinetic and equilibrium measurements show a moderate oxygen affinity (P 50 ϳ0.6 torr) and no cooperativity. The histidine binding affinity is 100-fold lower than in neuroglobin. Phylogenetic analysis demonstrates a clustering of the S. solidissima nerve Hb with mollusc Hbs and myoglobins, but not with the vertebrate neuroglobins. We conclude that invertebrate nerve Hbs expressed at high levels are, despite the hexacoordinate nature of their heme iron, not essentially different from other intracellular Hbs. They most likely fulfill a myoglobin-like function and enhance oxygen supply to the neurons.The recent discovery of globin proteins in the nerve cells of mammals and other vertebrates (1) has created much interest in unraveling the cellular functions and potential biomedical implications of these oxygen binding molecules in the metabolism of the vertebrate nervous system (2). Historically, however, "nerve hemoglobins" (nHbs) 4 were first observed in invertebrate taxa. In 1872, Lankester had already recorded the brilliant red color of the ganglia of the polychaete annelid Aphrodite aculeata (3). Since then, nHbs have also been found in, or associated with, nerve tissues of several other invertebrate taxa, such as molluscs, arthropods, nemerteans, and nematode species (4, 5). Of these, only the nHbs of A. aculeata (6) and the nemertean worm Cerebratulus lacteus (7) have been characterized at the molecular level.With few exceptions (e.g. in air-breathing gastropods), the invertebrate nHbs are expressed at high concentrations (in the mM range) and have therefore been suggested to support nerve function by mediating O 2 storage and/or transport during temporary hypoxia (4). For example, in the gastropod mollusc Aplysia depilans, the oxygenation state of the nHb was correlated with the electrical activity of the neural ganglia, and firing was shown to be proportional to the degree of oxygenation of the globin (8). The nHb in the nerve bundles of the bivalve mollusc Tellina alternata was reported to extend the time of O 2 delivery to the nerves during anoxic periods by as much as 30 min, whereas this effect was not demonstrable in the nerves of a related clam species Tagelius plebeius, which lack the nHb (9). In many cases, the nHbs appear to be specifically expressed in the glial cells surr...

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Section: Resultsmentioning

confidence: 99%

The Nerve Hemoglobin of the Bivalve Mollusc Spisula solidissima

Dewilde

Ebner

Vinck

et al. 2006

Journal of Biological Chemistry

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“…Hb Niigata [β1Val → Leu, with complete retention of the initiator Met and 24% acetylation of the aminoterminal Met] is a new variant found in Japan (Ohba et al, 1997), and MS technology contributed to demonstrating the acetylation of the substituted Met at the N ‐terminal of its β‐subunit. Lacan et al (2002) showed total acetylation at the α‐subunit N ‐terminal substituted amino acid using ESI‐MS. We detected three different amino acids in β67 (Miyazaki et al, 1996; Kano et al, 2004), Val, Met, and Asp, in a case initially reported as Hb Bristol [β67Val → Asp], and found another case with this variant.…”

Section: Abnormal Hemoglobin (Hemoglobin Variant)mentioning

confidence: 99%

Detection and characterization of variant and modified structures of proteins in blood and tissues by mass spectrometry

Shimizu

Nakanishi

Miyazaki

2006

Mass Spectrometry Reviews

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Some variant proteins cause diseases, and some diseases result in increases of proteins with abnormally modified structures. The detection, characterization, and estimation of the relative amounts of protein variants and abnormally modified proteins are important for clinical diagnosis and for elucidation of the mechanisms of the pathogenesis of diseases. Analysis of the covalent structures of proteins using matrix‐assisted laser desorption time‐of‐flight mass spectrometry (MALDI‐TOF‐MS) and liquid chromatography‐electrospray ionization MS (LC‐ESI‐MS), which had been developed by the early 1990s, have largely replaced analyses by conventional protein chemistry. Here, we review the detection and characterization of hemoglobin variants, HbA1c measurement, detection of carbohydrate‐deficient transferrin, and identification of variants of transthyretin (TTR) and Cu/Zn‐superoxide dismutase (SOD‐1) using soft ionization MS. We also propose the diagnostic application of the signals of modified forms of TTR, that is, S‐sulfonated TTR and S‐homocysteinyl TTR. The relative peak height ratio of the abnormal/normal components gives valuable information about the instability of variants and enables the detection of unstable Hb subunits or thalassemia heterozygotes. We found unique modified structures of TTR that suggested changes in amyloid fibrils. © 2006 Wiley Periodicals, Inc.

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Haemoglobin and the Genetics of Haemoglobin Synthesis

Bain¹

2006

Haemoglobinopathy Diagnosis

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New α2 globin chain variant with low oxygen affinity affecting the N‐terminal residue and leading to N‐acetylation [Hb Lyon‐Bron α 1(NA1)Val→Ac‐Ala]

Cited by 13 publications

References 17 publications

The Nerve Hemoglobin of the Bivalve Mollusc Spisula solidissima

The Nerve Hemoglobin of the Bivalve Mollusc Spisula solidissima

Detection and characterization of variant and modified structures of proteins in blood and tissues by mass spectrometry

Haemoglobin and the Genetics of Haemoglobin Synthesis

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