Publications by authors named "Gratzer W"

Spectrin tetramers of the membranes of enucleated mammalian erythrocytes play a critical role in red blood cell survival in circulation. One of the spectrins, αI, emerged in mammals with enucleated red cells after duplication of the ancestral α-spectrin gene common to all animals. The neofunctionalized αI-spectrin has moderate affinity for βI-spectrin, whereas αII-spectrin, expressed in nonerythroid cells, retains ancestral characteristics and has a 10-fold higher affinity for βI-spectrin.

View Article and Find Full Text PDF

The Community Centered Family Health History project was initiated to create accessible family health history tools produced by and for the community. The project goal was to promote increased community engagement in health education by encouraging conversations among family members that would translate knowledge of family health history into healthy lifestyle choices. As one of seven community partners, Iona College participated in customizing and beta-testing the Does It Run in the Family? toolkit.

View Article and Find Full Text PDF

Spectrins comprise α- and β-subunits made up predominantly of a series of homologous repeating units of about 106 amino acids; the α- and β-chains form antiparallel dimers by lateral association, and tetramers through head-to-head contacts between the dimers. Here we consider the first of these interactions. (1) We confirm earlier observations, showing that the first two paired repeats (βIR1 with αIR21, and βIR2 with αRI20) at one end of the erythroid spectrin (αIβI) dimer are necessary and sufficient to unite the chains; (2) we resolve a conflict in published reports by showing that the strength of the interaction is considerably increased on adding the adjoining pair of repeats (βIR3-αIR19); (3) in brain (αIIβII) spectrin the first two pairs of repeats are similarly essential and sufficient for heterodimer formation; (4) this interaction is ~60-fold stronger than that in the erythroid counterpart, but no enhancement can be detected on addition of three further pairs of repeats; (5) formation of a tight αIβI dimer probably depends on structural coupling of the first two repeats in each chain; (6) an analysis of the sequences of the strongly interacting repeats, βIR1, βIIR1, αIR21 and αIIR20 and repeats in α-actinin, which also interact very strongly in forming an antiparallel dimer, affords a possible explanation for the different properties of the two spectrin isoforms in respect of the stability of the inter-chain interactions, and also suggests the evolutionary path by which the erythroid and non-erythroid sequences diverged.

View Article and Find Full Text PDF

Spectrin tetramer is the major structural member of the membrane-associated skeletal network of red cells. We show here that disruption of the spectrin-ankyrin-band 3 link to the membrane leads to dissociation of a large proportion of the tetramers into dimers. Noncovalent perturbation of the linkage was induced by a peptide containing the ankyrin-binding site of the spectrin beta-chain, and covalent perturbation by treatment with the thiol reagent, N-ethylmaleimide (NEM).

View Article and Find Full Text PDF

We have analyzed the fluctuations of the red blood cell membrane in both the temporal ((omega(s(-1))) and spatial (q(m(-1))) frequency domains. The cells were examined over a range of osmolarities leading to cell volumes from 50% to 170% of that in the isotonic state. The fluctuations of the isotonic cell showed an approximately q(-3)-dependence, indicative of a motion dominated by bending, with an inferred bending modulus of approximately 9 x 10(-19) J.

View Article and Find Full Text PDF

The malaria parasite Plasmodium falciparum releases the ring-infected erythrocyte surface antigen (RESA) inside the red cell on entry. The protein migrates to the host cell membrane, where it binds to spectrin, but neither the nature of the interaction nor its functional consequences have previously been defined. Here, we identify the binding motifs involved in the interaction and describe a possible function.

View Article and Find Full Text PDF

The different genes that encode mammalian spectrins give rise to proteins differing in their apparent stiffness. To explore this, we have compared the thermal stabilities of the structural repeats of brain spectrin subunits (alphaII and betaII) with those of erythrocyte spectrin (alphaI and betaI). The unfolding transition midpoints (T(m)) of the 36 alphaII- and betaII-spectrin repeats extend between 24 and 82 degrees C, with an average higher by some 10 degrees C than that of the alphaI- and betaI-spectrin repeats.

View Article and Find Full Text PDF

The ternary complex of spectrin, actin, and 4.1R (human erythrocyte protein 4.1) defines the nodes of the erythrocyte membrane skeletal network and is inseparable from membrane stability under mechanical stress.

View Article and Find Full Text PDF

The two polypeptide chains of the erythroid spectrin heterodimer contain between them 36 structural repeating modules, which can function as independently folding units. We have expressed all 36 and determined their thermal stabilities. These vary widely, with unfolding transition mid-points (T(m)) ranging from 21 to 72 degrees C.

View Article and Find Full Text PDF

Mammalian red blood cells, unlike those of other vertebrates, must withstand the rigors of circulation in the absence of new protein synthesis. Key to this is plasma membrane elasticity deriving from the protein spectrin, which forms a network on the cytoplasmic face. Spectrin is a tetramer (alphabeta)(2), made up of alphabeta dimers linked head to head.

View Article and Find Full Text PDF

The ternary complex of spectrin, F-actin, and protein 4.1R defines the erythrocyte membrane skeletal network, which governs the stability and elasticity of the membrane. It has been shown that both 4.

View Article and Find Full Text PDF

Trofim Lysenko was a Ukrainian peasant whose malign influence dominated biology in the Soviet Union and its imperium through most of Stalin's reign. Lysenko owed his ascendancy to repeated promises that he would rescue Soviet agriculture from the catastrophic state into which it had sunk, following Stalin's disastrous policy of collectivisation of the farms, and a succession of bad harvests. He claimed to have devised methods of imposing desirable hereditary characteristics on plants, and even of converting one species into another at will.

View Article and Find Full Text PDF

Erythroid and neuronal spectrin (fodrin) are both known to interact strongly with the aminophospholipids that occur in the inner leaflet of plasma membranes. In erythroid spectrin the positions of the binding sites within the constituent (alphaI and betaI) polypeptide chains have been defined, and also the importance of the lipid interaction in regulating the properties of the membrane. Here we report the locations of the corresponding binding sites in the alphaII and betaII chains that make up the fodrin molecule.

View Article and Find Full Text PDF

The erythrocyte membrane is a composite structure consisting of a lipid bilayer tethered to the spectrin-based membrane skeleton. Two complexes of spectrin with other proteins are known to participate in the attachment. Spectrin has also been shown to interact with phosphatidylserine (PS), a component of the lipid bilayer, which is confined to its inner leaflet.

View Article and Find Full Text PDF

The red cell membrane derives its elasticity and resistance to mechanical stresses from the membrane skeleton, a network composed of spectrin tetramers. These are formed by the head-to-head association of pairs of heterodimers attached at their ends to junctional complexes of several proteins. Here we examine the dynamics of the spectrin dimer-dimer association in the intact membrane.

View Article and Find Full Text PDF

We have used optical tweezers to study the elasticity of red cell membranes; force was applied to a bead attached to a permeabilized spherical ghost and the force-extension relation was obtained from the response of a second bead bound at a diametrically opposite position. Interruption of the skeletal network by dissociation of spectrin tetramers or extraction of the actin junctions engendered a fourfold reduction in stiffness at low applied force, but only a twofold change at larger extensions. Proteolytic scission of the ankyrin, which links the membrane skeleton to the integral membrane protein, band 3, induced a similar effect.

View Article and Find Full Text PDF

We have examined the properties and interactions of expressed polypeptide fragments from the N-terminus of the alpha-chain and the C-terminus of the beta-chain of human erythroid spectrin. Each polypeptide comprises one complete structural repeating unit, together with the incomplete repeat that interacts with its partner when spectrin tetramers are formed. The shared repeat thus generated is made up of two helices from the C-terminal part of the beta-chain and one helix from the N-terminus of the alpha-chain.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessionk61kr0l5qeg3bip42vhkhhiotcqp7idq): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once