04血红蛋白和免疫球蛋白2016

肌红蛋白: myoglobin-oxygen storage protein
globin (珠蛋白) in complex with heme (血红素)
Myoglobin and hemoglobin may be the most-studied and best-understood proteins. These molecules illustrate almost every aspect of that most central of biochemical processes: the reversible binding of a ligand to a protein. This classic model of protein function tells us a great deal about how proteins work.
1) Kendrew, JC. Bodo, G. Dintzis, HM. Parrish, RG. Wyckoff, H. and Phillips DC. (1958). "A ThreeDimensional Model of the Myoglobin Molecule Obtained by X-Ray Analysis". Nature 181 (4610): 662–666. 2) Perutz, M.F.; Rossmann, M.G.; Cullis, A.F.; Muirhead, H.; Will, G.; North, A.C.T. (1960). "Structure of H". Nature 185 (4711): 416–422. 3) Perutz MF (November 1960). "Structure of hemoglobin". Brookhaven symposia in biology 13: 165–83.
H207/H269 phosphorylation
LicT wt (inactive)
LicT mutant (active) H207D/H269D
2、Reversible Binding of a Ligand to a Protein: 肌红蛋白和血红蛋白
血红蛋白: hemoglobin-oxygen transport protein(α2β2 in complex with 4 hemes)
本次作业（第三次作业）
1. 海拔高度调控别构效应子BPG浓度的分子 基础（或可以理解为海拔高度如何决定代 谢产物BPG的浓度）。 免疫记忆的分子基础。
2.
1、Concepts 基本概念
配基(ligand): A molecule bound reversibly by a protein is called a ligand. A ligand may be any kind of molecule, including another protein. A ligand binds at a site on the protein called the binding site, which is complementary to the ligand in size, shape, charge, and hydrophobic or hydrophilic character.
Intermolecular signal transduction In a multisubunit protein, a conformational change in one subunit often affects the conformation of other subunits.
§2.4 蛋白质的结构和功能
1、Concepts 基本概念
2、Reversible Binding of a Ligand to a Protein:
肌红蛋白和血红蛋白
3、Complementary Interactions between Proteins and Ligands: 免疫系统和免疫球蛋白
Research history
In 1840, the oxygen-carrying protein haemoglobin was discovered by Hü nefeld. In 1851, Otto Funke published a series of articles in which he described growing hemoglobin crystals by successively diluting red blood cells with a solvent such as pure
Types in humans Hemoglobin variants are a part of the normal embryonic and fetal development, but may also be pathologic mutant forms of hemoglobin in a population, caused by variations in genetics. Some variants such as sickle-cell anemia are responsible for diseases (hemoglobinopathies). Other variants cause no detectable pathology (nonpathological variants).
变构效应/别构效应
Interactions between ligands and proteins may be regulated, usually through specific interactions with one or more additional ligands. These other ligands may cause conformational changes in the protein that affect the binding of the first ligand. (for example, the case of BPG) Allosteric (变构效应) - an effect that affects the activity of one part of an enzyme (such as an active site) by the binding of a molecule at a different site (regulatory site) at a different location on the enzyme.
蛋白质的柔性 (Proteins are flexible)
Changes in conformation may be subtle, reflecting molecular vibrations and small movements of amino acid residues throughout the protein. A protein flexing (挠动) in this way is sometimes sa binding of a protein and ligand is often coupled to a conformational change in the protein that makes the binding site more complementary to the ligand, permitting tighter binding. The structural adaptation that occurs between protein and ligand is called induced fit (诱导契合).
Genetics 1) The sequences of hemoglobins differ between species. 2) Even within a species, different variants of hemoglobin exist. 3) Mutations in the genes for the hemoglobin protein in a species result in hemoglobin variants, some of these mutant forms of hemoglobin
Grd19/SNX3 Grd19PtdIn(3)P α2
α1’
α2
β3 β2 α4 β1
C
α1
C
β3 α4 β2 α1
N
α3
β1
α3
N
Grd19/SNX3
1 33 PX domain 158 162
Kd=0.15~0.5 µM
phosphatidylinositol-3-phosphate PtdIn(3)P 磷脂酰肌醇-3-磷酸
cause a group of hereditary diseases termed the hemoglobinopathies. 4) The best known is sickle-cell disease, which was the first human disease whose mechanism was understood at the molecular level. 5) A (mostly) separate set of diseases called thalassemias involves underproduction of normal and sometimes abnormal hemoglobins, through problems and mutations in globin gene regulation. 6) All these diseases produce anemia.