Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
ANALYSIS OF THE STABILITY OF HEMOGLOBIN-S DOUBLE STRANDS
Autore:
MU XQ; MAKOWSKI L; MAGDOFFFAIRCHILD B;
Indirizzi:
FLORIDA STATE UNIV,INST MOL BIOPHYS TALLAHASSEE FL 32306 FLORIDA STATE UNIV,INST MOL BIOPHYS TALLAHASSEE FL 32306 COLUMBIA UNIV,COLL PHYS & SURG,DEPT MED NEW YORK NY 10025 ST LUKES ROOSEVELT HOSP,DIV HEMATOL,MED SERV NEW YORK NY 10025
Titolo Testata:
Biophysical journal
fascicolo: 1, volume: 74, anno: 1998,
pagine: 655 - 668
SICI:
0006-3495(1998)74:1<655:AOTSOH>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
SICKLE-CELL HEMOGLOBIN; REFINED CRYSTAL-STRUCTURE; DEOXYHEMOGLOBIN-S; INTERMOLECULAR CONTACTS; FIBERS; PROTEIN; RESOLUTION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
X.Q. Mu et al., "ANALYSIS OF THE STABILITY OF HEMOGLOBIN-S DOUBLE STRANDS", Biophysical journal, 74(1), 1998, pp. 655-668

Abstract

The deoxyhemoglobin S (deoxy-HbS) double strand is the fundamental building block of both the crystals of deoxy-HbS and the physiologicallyrelevant fibers present within sickle cells. To use the atomic-resolution detail of the hemoglobin-hemoglobin interaction known from the crystallography of HbS as a basis for understanding the interactions in the fibers, it is necessary to define precisely the relationship between the straight double strands in the crystal and the twisted, helicaldouble strands in the fibers. The intermolecular contact conferring the stability of the double strand in both crystal and fiber is betweenthe beta 6 valine on one HbS molecule and residues near the EF cornerof an adjacent molecule. Models for the helical double strands were constructed by a geometric transformation from crystal to fiber that preserves this critical interaction, minimizes distortion, and makes thetransformation as smooth as possible. From these models, the energy of association was calculated over the range of all possible helical twists of the double strands and all possible-distances of the double strands from the fiber axis. The calculated association energies reflectthe fact that the axial interactions decrease as the distance betweenthe double strand and the fiber axis increases, because of the increased length of the helical path taken by the double strand. The lateralinteractions between HbS molecules in a double strand change relatively little between the crystal and possible helical double strands. If the twist of the fiber or the distance between the double strand and the fiber axis is too great, the lateral interaction is broken by intermolecular contacts in the region around the beta 6 valine. Consequently, the geometry of the beta 6 valine interaction and the residues surrounding it severely restricts the possible helical twist, radius, and handedness of helical aggregates constructed from the double strands. The limitations defined by this analysis establish the structural basis for the right-handed twist observed in HbS fibers and demonstrates that for a subunit twist of 8 degrees, the fiber diameter cannot be more than similar to 300 Angstrom, consistent with electron microscope observations. The energy of interaction among HbS molecules in a double strand is very slowly varying with helical pitch, explaining the variable pitch observed in HbS fibers. The analysis results in a model for the HbS double strand, for use in the analysis of interactions betweendouble strands and for refinement of models of the HbS fibers againstx-ray diffraction data.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 10:34:21