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1、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2.4 蛋白质的结构和功能本次作业（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）。 2.免疫记忆的分子基础。配基(ligand): A molecule bound reversibly by a protein is called a ligand
2、. 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.1、Concepts 基本概念The binding of a protein and ligand is often coupled
3、 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).In a multisubunit protein, a conformational change in one subunit often a
4、ffects the conformation of other subunits.Intermolecular signal transduction 结合常数解离常数低解离常数与亲和层析Enzymes represent a special case of protein function. Enzymes bind and chemically transform other molecules- they catalyze reactions. The molecules acted upon by enzymes are called reaction substrates (底物)
5、 rather than ligands, and the substrate- binding site is called the catalytic site (催化位点) or active site (活性位点).底物和活性位点Interactions between ligands and proteins may be regulated, usually through specific interactions with one or more additional ligands. These other ligands may cause conformational c
6、hanges 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
7、 enzyme. 变构效应/别构效应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 said to “breathe” Grd19/SNX31 12233112233441CNNCGrd19- PtdIn(3)P蛋白质的柔性 (Proteins are flexible) G
8、rd19/SNX31 33 PX domain 158 162phosphatidylinositol-3-phosphate PtdIn(3)P 磷脂酰肌醇-3-磷酸Kd=0.150.5 MActive FormChanges in conformation may also be quite dramatic, with major segments of the protein structure moving as much as several nanometers. Specific conformational changes are frequently essential t
9、o a proteins function.LicT mutant (active) H207D/H269DLicT wt (inactive)H207/H269 phosphorylation2、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 (22 in complex with 4 hemes)肌红蛋白: myoglobin-oxygen storage proteinMyoglobin and hemoglobin may be the mos
10、t-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.globin (珠蛋白) in complex with heme
11、 (血红素) In 1840, the oxygen-carrying protein haemoglobin was discovered by Hnefeld.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 water, alcohol or ether, followed by slow evapor
12、ation of the solvent from the resulting protein solution. In 1958, John Kendrew and associates successfully determined the structure of myoglobin by high-resolution X-ray crystallography. In 1959, Max Perutz determined the molecular structure of hemoglobin by X-ray crystallography. For this discover
13、y, John Kendrew shared the 1962 Nobel Prize in chemistry with Max Perutz.1) Kendrew, JC. Bodo, G. Dintzis, HM. Parrish, RG. Wyckoff, H. and Phillips DC. (1958). “A Three- Dimensional Model of the Myoglobin Molecule Obtained by X-Ray Analysis“. Nature 181 (4610): 662666. 2) Perutz, M.F.; Rossmann, M.
14、G.; Cullis, A.F.; Muirhead, H.; Will, G.; North, A.C.T. (1960). “Structure of H“. Nature 185 (4711): 416422. 3) Perutz MF (November 1960). “Structure of hemoglobin“. Brookhaven symposia in biology 13: 16583. Research history1) The sequences of hemoglobins differ between species. 2) Even within a spe
15、cies, 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 cause a group of hereditary diseases termed the hemoglobinopathies. 4) The best known is sickle-cell disease, which
16、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.GeneticsTypes in humans Hemoglobin variants are a part o
