HUMAN EMBRYONIC, FETAL, & ADULT HBS HAVE DIFFERENT SUBUNIT INTERFACE STRENGTHS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 不同类型的自然产生的正常人类血红蛋白在配基(CO或氧)状态下，其四聚体-二聚体亚单位界面强度(稳定性)差异三个数量级。胚胎Zeta亚基的存在导致四聚体-二聚体界面平均比含有成年α-亚基的相应的血红蛋白弱20倍。这些血红蛋白的二聚体-单体界面的强度相差至少500倍；如果它们含有Zeta亚基，并且与以β(4)(HBH)形式添加的β-亚基交换的速度明显快于具有α-亚基的界面，则此类界面是弱的。亚基交换发生在二聚体的水平上，尽管四聚体的形成反过来影响可用于交换的二聚体的量。亚基类型之间的竞争发生了，因此一对较弱的胚胎血红蛋白可以交换亚基，形成较强的胎儿和成人血红蛋白。二聚体强度按Hb Portland-2(Zeta(2)beta(2))&lt；Hb Portland-1(Zeta(2)Gamma(2))近似等于Hb Gower-1(Zeta(2)epsilon(2))&lt；Hb Gower-2(α(2)epsilon(2))&lt；HbF(1)&lt；HbF(Alpha(2)Gamma(2))&lt；Hba(2)(α(2)Delta(2))，即从胚胎到胎儿再到成人型，代表着从较弱的单体-单体亚单位接触到较强的成熟。这个递增的顺序概括了珠蛋白表达的发育顺序(胚胎--&gt；胎儿--&gt；成体)，这表明亚基本身关于它们与竞争亚基形成的界面的强度的内在结合特性在蛋白质组装和网络的动力学中发挥着重要作用。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.