Subunit Dissociation of the Unstable Hemoglobin Bibba (α2136 ro (H19)β2)

A new unstable hemoglobin with high oxygen affinity, Hb Toyoake: beta 142 (H20) Ala replaced by Pro, was found in Japanese male with a normal blood hemoglobin level, shortened red cell survival, and increased plasma erythropoietin. Hemoglobin studies showed heat and isopropanol instability, and an increased tendency to heme loss and to subunit dissociation. Electrophoresis of whole hemolysate showed inconstant abnormal bands with reduced mobilities due to progressive heme loss during the in vitro procedure. Isolated Hb Toyoake with normal heme content migrated slightly faster than HbA. Oxygen affinity of red cells was elevated with P50 of 17.0 mm Hg at pH 7.4 and 37 degrees C (normal 25.0 mm Hg). Studies on hemolysate implied that Hb Toyoake had an almost normal Bohr effect, a diminished cooperativity, and a reduced response to inositol hexaphosphate. These multiple abnormalities are associated with a substitution of Pro for beta 142 Ala, resulting in disruption of the H-helix and the adjacent C-terminal portion of beta chain, which contain residues crucial for normal oxygen binding.

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Hb Toyoake: beta 142 (H20) Ala replaced by Pro. A new unstable hemoglobin with high oxygen affinity

Blood ◽

10.1182/blood.v57.4.697.697 ◽

1981 ◽

Vol 57 (4) ◽

pp. 697-704 ◽

Cited By ~ 22

Author(s):

M Hirano ◽

Y Ohba ◽

K Imai ◽

T Ino ◽

Y Morishita ◽

...

Keyword(s):

Oxygen Affinity ◽

High Oxygen ◽

Oxygen Binding ◽

Subunit Dissociation ◽

Japanese Male ◽

Red Cell Survival ◽

High Oxygen Affinity ◽

Multiple Abnormalities ◽

Unstable Hemoglobin

Abstract A new unstable hemoglobin with high oxygen affinity, Hb Toyoake: beta 142 (H20) Ala replaced by Pro, was found in Japanese male with a normal blood hemoglobin level, shortened red cell survival, and increased plasma erythropoietin. Hemoglobin studies showed heat and isopropanol instability, and an increased tendency to heme loss and to subunit dissociation. Electrophoresis of whole hemolysate showed inconstant abnormal bands with reduced mobilities due to progressive heme loss during the in vitro procedure. Isolated Hb Toyoake with normal heme content migrated slightly faster than HbA. Oxygen affinity of red cells was elevated with P50 of 17.0 mm Hg at pH 7.4 and 37 degrees C (normal 25.0 mm Hg). Studies on hemolysate implied that Hb Toyoake had an almost normal Bohr effect, a diminished cooperativity, and a reduced response to inositol hexaphosphate. These multiple abnormalities are associated with a substitution of Pro for beta 142 Ala, resulting in disruption of the H-helix and the adjacent C-terminal portion of beta chain, which contain residues crucial for normal oxygen binding.

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Pathways for penetration of iron and negative stain across the protein shell of ferritin: Ultrastructural perspectives

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100129693 ◽

1992 ◽

Vol 50 (2) ◽

pp. 1012-1013

Author(s):

William H. Massover

Keyword(s):

Outer Shell ◽

X Ray Diffraction ◽

Central Cavity ◽

X Ray ◽

Subunit Dissociation ◽

Negative Stain ◽

Analogous Question ◽

Protein Shell

Molecules of the metalloprotein, ferritin, have an outer shell comprised of a polymeric assembly of 24 polypeptide subunits (apoferritin). This protein shell encloses a hydrated space, the central cavity, within which up to several thousand iron atoms can be deposited as the biomineral, ferrihydrite. The actual pathway taken by iron moving across the protein shell is not known; an analogous question exists for the demonstrated entrance of negative stains into the central cavity. Intersubunit interstices at the 4-fold and 3-fold symmetry axes have been defined with x-ray diffraction, and were hypothesized to provide a pathway for penetration through the outer shell; however, since these channels are only 4Å in width, they are much too small to allow simple permeation of either hydrated iron or stain ions. A different hypothesis, based on studies of subunit dissociation from highly diluted ferritin, proposes that transient gaps in the protein shell are created by a rapid reversible subunit release and permit the direct passage of large ions into the central cavity.

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