Hb Foggia or  117(GH5)Phe -&gt; Ser : a new  2 globin allele affecting the  Hb-AHSP interaction

Lacerra, Giuseppina; Scarano, Clelia; Musollino, Gennaro; Flagiello, Angela; Pucci, Piero; Carestia, Clementina

doi:10.3324/haematol.11789

Cited by 21 publications

(23 citation statements)

References 9 publications

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“…5). Thus, these results are ambiguous, and it is unclear which disrupted interactions, AHSP:a H -chain or a 1 b 1 , give rise to the observed phenotypes (68,103). H subunits, but is not part of the interface with AHSP.…”

Section: Clinical Relevance Of Ahsp Functionmentioning

confidence: 86%

“…Marden and co-workers have suggested that AHSP-a H -chain interactions are impeded by a proline to serine mutation at position 119 of a H chains (P119S, Hb Groene Hart), which results in an a thalassemia phenotype (102). Another novel a H chain mutation (F117S, Hb Foggia) also results in a phenotype typical of a thalassemia (68). This mutation is predicted to disrupt favorable interactions with AHSP (34,68).…”

Section: Clinical Relevance Of Ahsp Functionmentioning

confidence: 99%

“…Another novel a H chain mutation (F117S, Hb Foggia) also results in a phenotype typical of a thalassemia (68). This mutation is predicted to disrupt favorable interactions with AHSP (34,68). Vasseur et al (103) have recently evaluated a set of clinically relevant a H chain mutations: H103L (Bronovo); C104Y (Sallanches); C104S (Oegstgeest); T108N (Bleuland); L109R (Suan Dok); L109Q; F117S (Foggia); P119S (Groene Hart); P119L (Diamant); and L129P (Utrecht).…”

Section: Clinical Relevance Of Ahsp Functionmentioning

confidence: 99%

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The Role of Alpha-Hemoglobin Stabilizing Protein in Redox Chemistry, Denaturation, and Hemoglobin Assembly

Mollan

Weiss

et al. 2010

Antioxidants & Redox Signaling

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Hemoglobin biosynthesis in erythrocyte precursors involves several steps. The correct ratios and concentrations of normal alpha (a) and beta (b) globin proteins must be expressed; apoproteins must be folded correctly; heme must be synthesized and incorporated into these globins rapidly; and the individual a and b subunits must be rapidly and correctly assembled into heterotetramers. These events occur on a large scale in vivo, and dysregulation causes serious clinical disorders such as thalassemia syndromes. Recent work has implicated a conserved erythroid protein known as Alpha-Hemoglobin Stabilizing Protein (AHSP) as a participant in these events. Current evidence suggests that AHSP enhances a subunit stability and diminishes its participation in harmful redox chemistry. There is also evidence that AHSP facilitates one or more early-stage post-translational hemoglobin biosynthetic events. In this review, recent experimental results are discussed in light of several current models describing globin subunit folding, heme uptake, assembly, and denaturation during hemoglobin synthesis. Particular attention is devoted to molecular interactions with AHSP that relate to a chain oxidation and the ability of a chains to associate with partner b chains. Antioxid. Redox Signal. 12, 219-232.

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Section: Clinical Relevance Of Ahsp Functionmentioning

confidence: 86%

Section: Clinical Relevance Of Ahsp Functionmentioning

confidence: 99%

Section: Clinical Relevance Of Ahsp Functionmentioning

confidence: 99%

See 1 more Smart Citation

The Role of Alpha-Hemoglobin Stabilizing Protein in Redox Chemistry, Denaturation, and Hemoglobin Assembly

Mollan

Weiss

et al. 2010

Antioxidants & Redox Signaling

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“…8,12,[25][26][27][28][29][30][31][32][33][34][35] We used the Globin Gene Server, published case reports, and crystallographic studies to identify naturally occurring ␣ globin gene mutations that alter amino acids at AHSP contact sites ( Figure 1A). 8 Some of these mutations occur at the ␣ 1 ␤ 1 interface and may also affect ␤ globin binding (Table 1; Figure 1) 8 (and www.rcsb.org).…”

Section: Resultsmentioning

confidence: 99%

“…Some ␣ globin variants contain amino acid substitutions at the AHSP-binding interface, which has been mapped by structural studies (see Globin Gene Server, http:// globin.cse.psu.edu). 8,9 Several reports describe clinically significant ␣ globin mutations that inhibit ␣ globin-AHSP interactions, including antiterminator mutations Hb Pakse and Hb Constant Springs 10,11 and missense mutations F117S (Hb Foggia) 12 and P119S (Hb Groene-Hart). 13 These studies suggest new mechanisms for hemoglobinopathies by identifying ␣ globin variants that may not be stabilized by AHSP in vivo.…”

Section: Introductionmentioning

confidence: 99%

Analysis of human α globin gene mutations that impair binding to the α hemoglobin stabilizing protein

Mollan

Butler

et al. 2009

Blood

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Alpha hemoglobin stabilizing protein (AHSP) reversibly binds nascent ␣ globin to maintain its native structure and facilitate its incorporation into hemoglobin A. Previous studies indicate that some naturally occurring human ␣ globin mutations may destabilize the protein by inhibiting its interactions with AHSP. However, these mutations could also affect hemoglobin A production through AHSP-independent effects, including reduced binding to ␤ globin. We analyzed 6 human ␣ globin variants with altered AHSP contact surfaces. Alpha globin amino acid substitutions H103Y, H103R, F117S, and P119S impaired interactions with both AHSP and ␤ globin. These mutations are destabilizing in biochemical assays and are associated with microcytosis and anemia in humans. By contrast, K99E and K99N ␣ globins bind ␤ globin normally but exhibit attenuated binding to AHSP. These mutations impair protein folding and expression in vitro and appear to be mildly destabilizing in vivo. In Escherichia coli and erythroid cells, ␣ globin K99E stability is rescued on coexpression with AHSP mutants in which binding to the abnormal globin chain is restored. Our results better define the biochemical properties of some ␣ globin variants and support the hypothesis that AHSP promotes ␣ globin chain stability during human erythropoiesis. (Blood. 2009;113:5961-5969)

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Faithful chaperones

Szołajska

Chroboczek

2011

Cell. Mol. Life Sci.

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This review describes the properties of some rare eukaryotic chaperones that each assist in the folding of only one target protein. In particular, we describe (1) the tubulin cofactors, (2) p47, which assists in the folding of collagen, (3) α-hemoglobin stabilizing protein (AHSP), (4) the adenovirus L4-100 K protein, which is a chaperone of the major structural viral protein, hexon, and (5) HYPK, the huntingtin-interacting protein. These various-sized proteins (102–1,190 amino acids long) are all involved in the folding of oligomeric polypeptides but are otherwise functionally unique, as they each assist only one particular client. This raises a question regarding the biosynthetic cost of the high-level production of such chaperones. As the clients of faithful chaperones are all abundant proteins that are essential cellular or viral components, it is conceivable that this necessary metabolic expenditure withstood evolutionary pressure to minimize biosynthetic costs. Nevertheless, the complexity of the folding pathways in which these chaperones are involved results in error-prone processes. Several human disorders associated with these chaperones are discussed.

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Hb Foggia or 117(GH5)Phe -> Ser : a new 2 globin allele affecting the Hb-AHSP interaction

Cited by 21 publications

References 9 publications

The Role of Alpha-Hemoglobin Stabilizing Protein in Redox Chemistry, Denaturation, and Hemoglobin Assembly

The Role of Alpha-Hemoglobin Stabilizing Protein in Redox Chemistry, Denaturation, and Hemoglobin Assembly

Analysis of human α globin gene mutations that impair binding to the α hemoglobin stabilizing protein

Faithful chaperones

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