Morrill Gene A, Kostellow Adele B
Department of Physiology and Biophysics, Albert Einstein College of Medicine Bronx, NY, USA.
Front Physiol. 2016 Sep 5;7:360. doi: 10.3389/fphys.2016.00360. eCollection 2016.
Globins contain one or more cavities that control or affect such functions as ligand movement and ligand binding. Here we report that the extended globin family [cytoglobin (Cygb); neuroglobin (Ngb); myoglobin (Mb); hemoglobin (Hb) subunits Hba(α); and Hbb(β)] contain either a transmembrane (TM) helix or pore-lining region as well as internal cavities. Protein motif/domain analyses indicate that Ngb and Hbb each contain 5 cholesterol- binding (CRAC/CARC) domains and 1 caveolin binding motif, whereas the Cygb dimer has 6 cholesterol-binding domains but lacks caveolin-binding motifs. Mb and Hba each exhibit 2 cholesterol-binding domains and also lack caveolin-binding motifs. The Hb αβ-tetramer contains 14 cholesterol-binding domains. Computer algorithms indicate that Cygb and Ngb cavities display multiple partitions and C-terminal pore-lining regions, whereas Mb has three major cavities plus a C-terminal pore-lining region. The Hb tetramer exhibits a large internal cavity but the subunits differ in that they contain a C-terminal TM helix (Hba) and pore-lining region (Hbb). The cavities include 43 of 190 Cygb residues, 38 of 151 of Ngb residues, 55 of 154 Mb residues, and 137 of 688 residues in the Hb tetramer. Each cavity complex includes 6 to 8 residues of the TM helix or pore-lining region and CRAC/CARC domains exist within all cavities. Erythrocyte Hb αβ-tetramers are largely cytosolic but also bind to a membrane anion exchange protein, "band 3," which contains a large internal cavity and 12 TM helices (5 being pore-lining regions). The Hba TM helix may be the erythrocyte membrane "band 3" attachment site. "Band 3" contributes 4 caveolin binding motifs and 10 CRAC/CARC domains. Cholesterol binding may create lipid-disordered phases that alter globin cavities and facilitate ligand movement, permitting ion channel formation and conformational changes that orchestrate anion and ligand (O2, CO2, NO) movement within the large internal cavities and channels of the globins.
珠蛋白含有一个或多个控制或影响配体移动和配体结合等功能的腔。在此我们报告，扩展的珠蛋白家族[细胞珠蛋白（Cygb）；神经珠蛋白（Ngb）；肌红蛋白（Mb）；血红蛋白（Hb）亚基Hba(α)和Hbb(β)]含有一个跨膜（TM）螺旋或孔衬区域以及内部腔。蛋白质基序/结构域分析表明，Ngb和Hbb各自含有5个胆固醇结合（CRAC/CARC）结构域和1个小窝蛋白结合基序，而Cygb二聚体有6个胆固醇结合结构域但缺乏小窝蛋白结合基序。Mb和Hba各自有2个胆固醇结合结构域，也缺乏小窝蛋白结合基序。Hbαβ四聚体含有14个胆固醇结合结构域。计算机算法表明，Cygb和Ngb的腔显示出多个分区和C端孔衬区域，而Mb有三个主要腔加上一个C端孔衬区域。Hb四聚体有一个大的内部腔，但亚基不同，因为它们含有一个C端TM螺旋（Hba）和孔衬区域（Hbb）。这些腔包括Cygb的190个残基中的43个、Ngb的151个残基中的38个、Mb的154个残基中的55个以及Hb四聚体的688个残基中的137个。每个腔复合体包括TM螺旋或孔衬区域的6至8个残基，并且所有腔中都存在CRAC/CARC结构域。红细胞Hbαβ四聚体主要位于胞质中，但也与一种膜阴离子交换蛋白“带3”结合，“带3”含有一个大的内部腔和12个TM螺旋（5个是孔衬区域）。Hba TM螺旋可能是红细胞膜“带3”的附着位点。“带3”有4个小窝蛋白结合基序和10个CRAC/CARC结构域。胆固醇结合可能会产生脂质无序相，从而改变珠蛋白腔并促进配体移动，允许离子通道形成和构象变化，从而协调阴离子和配体（O2、CO2、NO）在珠蛋白的大内部腔和通道内的移动。
