17656582

pubmed:Citation

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The different types of naturally occurring, normal human hemoglobins vary in their tetramer-dimer subunit interface strengths (stabilities) by three orders of magnitude in the liganded (CO or oxy) state. The presence of embryonic zeta-subunits leads to an average 20-fold weakening of tetramer-dimer interfaces compared to corresponding hemoglobins containing adult alpha-subunits. The dimer-monomer interfaces of these hemoglobins differ by at least 500-fold in their strengths; such interfaces are weak if they contain zeta-subunits and exchange with added beta-subunits in the form of beta(4) (HbH) significantly faster than do those with alpha-subunits. Subunit exchange occurs at the level of the dimer, although tetramer formation reciprocally influences the amount of dimer available for exchange. Competition between subunit types occurs so that pairs of weak embryonic hemoglobins can exchange subunits to form the stronger fetal and adult hemoglobins. The dimer strengths increase in the order Hb Portland-2 (zeta(2)beta(2)) < Hb Portland-1 (zeta(2)gamma(2)) approximately equal Hb Gower-1 (zeta(2)epsilon(2)) < Hb Gower-2 (alpha(2)epsilon(2)) < HbF(1) < HbF (alpha(2)gamma(2)) < HbA(2) (alpha(2)delta(2)), i.e., from embryonic to fetal to adult types, representing maturation from weaker to stronger monomer-monomer subunit contacts. This increasing order recapitulates the developmental order in which globins are expressed (embryonic --> fetal --> adult), suggesting that the intrinsic binding properties of the subunits themselves regarding the strengths of interfaces they form with competing subunits play an important role in the dynamics of protein assemblies and networks.

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http://linkedlifedata.com/resource/pubmed/journal/9211750

http://linkedlifedata.com/resource/pubmed/chemical/Fetal Hemoglobin, http://linkedlifedata.com/resource/pubmed/chemical/Hemoglobin A2, http://linkedlifedata.com/resource/pubmed/chemical/Hemoglobins, http://linkedlifedata.com/resource/pubmed/chemical/Hemoglobins, Abnormal, http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits, http://linkedlifedata.com/resource/pubmed/chemical/hemoglobin Gower, http://linkedlifedata.com/resource/pubmed/chemical/hemoglobin Portland

Aug

pubmed-author:ChaitBrian TBT, pubmed-author:ManningJames MJM, pubmed-author:ManningLois RLR, pubmed-author:ManningRobert SRS, pubmed-author:PadovanJulio CJC, pubmed-author:PopowiczAnthonyA, pubmed-author:RussellJ EricJE

16

Y

2009-11-18