Short insertion in a hemoglobin chain: Hb Esch, an unstable alpha1 variant with duplication of the sequence Ala65-Leu-Thr-Asn68.
Hemoglobin (Hb) Esch, is an alpha1 variant, expressed at less than 5%, resulting from the duplication of the 12 nucleotides corresponding to CD65 through 68. The effect of this insertion is the repetition of the sequence Ala-Leu-Thr-Asn, which corresponds to the last turn of helix E. In this variant the presence of a one-turn elongated helix E causes instability and increased ligand affinity. Hb Esch was characterized by DNA sequencing and confirmed by electrospray mass spectrometry. Functional studies were performed by flash photolysis measurements on a fraction isolated by flatbed isoelectric focusing, which was enriched in the abnormal hemoglobin. Similar to other alpha chain variants due to short insertion (or deletion), Hb Esch probably results from a slipped mispairing mechanism. The stability of such modified proteins depends upon the region which is added or deleted and usually is more stable when involving a flexible loop or complete helix turn(s) near by.
Préhu
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INSERM U 468 and Laboratoire de Biochimie, Hôpital Henri Mondor, 94010 Creteil, France.
Groff
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Kalmes
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Golinska
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B
Riou
J
J
Prome
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Richelme-David
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Kiger
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L
Ducrocq
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Wajcman
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D000328:Adult; D000595:Amino Acid Sequence; D020440:Gene Duplication; D014644:Genetic Variation; D006454:Hemoglobins / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D016254:Mutagenesis, Insertional; D010446:Peptide Fragments / Q000235:genetics*; D011174:Portugal; D017085:alpha-Thalassemia / Q000175:diagnosis / Q000235:genetics
D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D010446:Peptide Fragments; C070077:alpha(A) globin