Identification of the Components of a Glycolytic Enzyme Metabolon on the Human Red Blood Cell Membrane

Puchulu-Campanella, Estela; Chu, Haiyan; Anstee, David J.; Galán, Jacob A.; Tao, W. Andy; Low, Philip S.

doi:10.1074/jbc.m112.428573

Cited by 104 publications

(110 citation statements)

References 59 publications

(57 reference statements)

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“…The concentration of soluble oxyHb and the presence of deoxyHb to interact with regulatory sites at the membrane have been proposed as key regulators of KCC activity. 24 In this context, the presence of crystals of HbC 25 at high oxygen tension and their dissolution at low oxygen tension may be important. The role of oxygen is clearly complicated in HbSC, and likely to differ depending on many dynamic factors, including pH, temperature and age of the red cell, but this study raises the possibility that oxygen supplementation may be harmful to patients with HbSC disease in some circumstances.…”

Section: Discussionmentioning

confidence: 99%

The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease

et al. 2015

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Section: Discussionmentioning

confidence: 99%

The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease

et al. 2015

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“…(Could this be the long-sought mechanism for splenic conditioning 89 in hereditary spherocytosis?). 78 In the cytoplasmic domain, the glycolytic enzymes PFK, aldolase, and G3PD bind to amino acids 1 to 23 at the N-terminus of band 3 and contact amino acids 356 to 384, 79 which are nearby in the folded protein. The enzymes are inactive when bound, 80 but are displaced and activated by deoxyhemoglobin (Hb), which also binds to the N-terminus, 81 or by phosphorylation of 2 tyrosines (Tyr21-P and Tyr8-P) within the binding sites.…”

Section: Bandmentioning

confidence: 99%

“…Functionally, it is 2 proteins 78 : (1) an N-terminal cytoplasmic, peripheral membrane protein that is a key attachment site for the membrane skeleton, glycolytic enzymes, and deoxyhemoglobin; and (2) a C-terminal integral membrane protein that forms the red cell anion-exchange channel and aids carbon dioxide transport (Figure 7 [78][79][80][81][82][83][84][85][86] ). The glycolytic enzymes form a metabolic complex (metabolon) extending from phosphofructokinase through lactic dehydrogenase.…”

Section: Bandmentioning

confidence: 99%

Anatomy of the red cell membrane skeleton: unanswered questions

Lux

2016

Blood

297

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The red cell membrane skeleton is a pseudohexagonal meshwork of spectrin, actin, protein 4.1R, ankyrin, and actin-associated proteins that laminates the inner membrane surface and attaches to the overlying lipid bilayer via band 3–containing multiprotein complexes at the ankyrin- and actin-binding ends of spectrin. The membrane skeleton strengthens the lipid bilayer and endows the membrane with the durability and flexibility to survive in the circulation. In the 36 years since the first primitive model of the red cell skeleton was proposed, many additional proteins have been discovered, and their structures and interactions have been defined. However, almost nothing is known of the skeleton’s physiology, and myriad questions about its structure remain, including questions concerning the structure of spectrin in situ, the way spectrin and other proteins bind to actin, how the membrane is assembled, the dynamics of the skeleton when the membrane is deformed or perturbed by parasites, the role lipids play, and variations in membrane structure in unique regions like lipid rafts. This knowledge is important because the red cell membrane skeleton is the model for spectrin-based membrane skeletons in all cells, and because defects in the red cell membrane skeleton underlie multiple hemolytic anemias.

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“…Sulfo-SBED derivatization of cdb3-PO 4 : untagged-cdb3-PO 4 was derivatized with sulfo-SBED in the dark following a previously published protocol (5,28).…”

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confidence: 99%

Global transformation of erythrocyte properties via engagement of an SH2-like sequence in band 3

Puchulu-Campanella

Turrini

2016

Proc. Natl. Acad. Sci. U.S.A.

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Src homology 2 (SH2) domains are composed of weakly conserved sequences of ∼100 aa that bind phosphotyrosines in signaling proteins and thereby mediate intra-and intermolecular protein-protein interactions. In exploring the mechanism whereby tyrosine phosphorylation of the erythrocyte anion transporter, band 3, triggers membrane destabilization, vesiculation, and fragmentation, we discovered a SH2 signature motif positioned between membrane-spanning helices 4 and 5. Evidence that this exposed cytoplasmic sequence contributes to a functional SH2-like domain is provided by observations that: (i) it contains the most conserved sequence of SH2 domains, GSFLVR; (ii) it binds the tyrosine phosphorylated cytoplasmic domain of band 3 (cdb3-PO 4 ) with K d = 14 nM; (iii) binding of cdb3-PO 4 to erythrocyte membranes is inhibited both by antibodies against the SH2 signature sequence and dephosphorylation of cdb3-PO 4 ; (iv) label transfer experiments demonstrate the covalent transfer of photoactivatable biotin from isolated cdb3-PO 4 (but not cdb3) to band 3 in erythrocyte membranes; and (v) phosphorylation-induced binding of cdb3-PO 4 to the membrane-spanning domain of band 3 in intact cells causes global changes in membrane properties, including (i) displacement of a glycolytic enzyme complex from the membrane, (ii) inhibition of anion transport, and (iii) rupture of the band 3-ankyrin bridge connecting the spectrin-based cytoskeleton to the membrane. Because SH2-like motifs are not retrieved by normal homology searches for SH2 domains, but can be found in many tyrosine kinase-regulated transport proteins using modified search programs, we suggest that related cases of membrane transport proteins containing similar motifs are widespread in nature where they participate in regulation of cell properties.SH2 domain motif | tyrosine phosphorylation | erythrocyte glycolysis | anion exchanger 1 | regulation of transport proteins P rotein tyrosine phosphorylation is involved in the regulation of most cellular process, including proliferation, survival, differentiation, responses to stress, and control of cell shape/motility (1). Whereas phosphotyrosine binding (PTB) domains may mediate association with tyrosine-containing sequences regardless of their phosphorylation state, Src homology 2 (SH2) domains promote protein association only when critical tyrosine residues become phosphorylated. This strict dependence on tyrosine phosphorylation creates a molecular switch that can be sensitively controlled by upstream tyrosine kinases (1). Whereas some SH2 domains facilitate association between heterologous proteins in a signaling pathway, others mediate intrapolypeptide interactions that change protein conformation and thereby alter signaling function (2). In all cases, association between the SH2 domain and the interacting phosphotyrosine involves formation of weak interactions between a highly conserved G(S/T)FLVR sequence of the SH2 domain and the phosphate present on the phosphorylated tyrosine. To date, all 120 known SH2 domain...

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Identification of the Components of a Glycolytic Enzyme Metabolon on the Human Red Blood Cell Membrane

Cited by 104 publications

References 59 publications

The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease

The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease

Anatomy of the red cell membrane skeleton: unanswered questions

Global transformation of erythrocyte properties via engagement of an SH2-like sequence in band 3

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