1j40
From Proteopedia
Direct observation of photolysis-induced tertiary structural changes in human haemoglobin; Crystal structure of alpha(Ni)-beta(Fe-CO) hemoglobin (laser unphotolysed)
Structural highlights
Disease[HBB_HUMAN] Defects in HBB may be a cause of Heinz body anemias (HEIBAN) [MIM:140700]. This is a form of non-spherocytic hemolytic anemia of Dacie type 1. After splenectomy, which has little benefit, basophilic inclusions called Heinz bodies are demonstrable in the erythrocytes. Before splenectomy, diffuse or punctate basophilia may be evident. Most of these cases are probably instances of hemoglobinopathy. The hemoglobin demonstrates heat lability. Heinz bodies are observed also with the Ivemark syndrome (asplenia with cardiovascular anomalies) and with glutathione peroxidase deficiency.[1] [2] [3] [4] Defects in HBB are the cause of beta-thalassemia (B-THAL) [MIM:613985]. A form of thalassemia. Thalassemias are common monogenic diseases occurring mostly in Mediterranean and Southeast Asian populations. The hallmark of beta-thalassemia is an imbalance in globin-chain production in the adult HbA molecule. Absence of beta chain causes beta(0)-thalassemia, while reduced amounts of detectable beta globin causes beta(+)-thalassemia. In the severe forms of beta-thalassemia, the excess alpha globin chains accumulate in the developing erythroid precursors in the marrow. Their deposition leads to a vast increase in erythroid apoptosis that in turn causes ineffective erythropoiesis and severe microcytic hypochromic anemia. Clinically, beta-thalassemia is divided into thalassemia major which is transfusion dependent, thalassemia intermedia (of intermediate severity), and thalassemia minor that is asymptomatic.[5] Defects in HBB are the cause of sickle cell anemia (SKCA) [MIM:603903]; also known as sickle cell disease. Sickle cell anemia is characterized by abnormally shaped red cells resulting in chronic anemia and periodic episodes of pain, serious infections and damage to vital organs. Normal red blood cells are round and flexible and flow easily through blood vessels, but in sickle cell anemia, the abnormal hemoglobin (called Hb S) causes red blood cells to become stiff. They are C-shaped and resembles a sickle. These stiffer red blood cells can led to microvascular occlusion thus cutting off the blood supply to nearby tissues. Defects in HBB are the cause of beta-thalassemia dominant inclusion body type (B-THALIB) [MIM:603902]. An autosomal dominant form of beta thalassemia characterized by moderate anemia, lifelong jaundice, cholelithiasis and splenomegaly, marked morphologic changes in the red cells, erythroid hyperplasia of the bone marrow with increased numbers of multinucleate red cell precursors, and the presence of large inclusion bodies in the normoblasts, both in the marrow and in the peripheral blood after splenectomy.[6] Function[HBB_HUMAN] Involved in oxygen transport from the lung to the various peripheral tissues.[7] LVV-hemorphin-7 potentiates the activity of bradykinin, causing a decrease in blood pressure.[8] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman Hb, an alpha2beta2 tetrameric oxygen transport protein that switches from a T (tense) to an R (relaxed) quaternary structure during oxygenation, has long served as a model for studying protein allostery in general. Time-resolved spectroscopic measurements after photodissociation of CO-liganded Hb have played a central role in exploring both protein dynamical responses and molecular cooperativity, but the direct visualization and the structural consequences of photodeligation have not yet been reported. Here we present an x-ray study of structural changes induced by photodissociation of half-liganded T-state and fully liganded R-state human Hb at cryogenic temperatures (25-35 K). On photodissociation of CO, structural changes involving the heme and the F-helix are more marked in the alpha subunit than in the beta subunit, and more subtle in the R state than in the T state. Photodeligation causes a significant sliding motion of the T-state beta heme. Our results establish that the structural basis of the low affinity of the T state is radically different between the subunits, because of differences in the packing and chemical tension at the hemes. Direct observation of photolysis-induced tertiary structural changes in hemoglobin.,Adachi S, Park SY, Tame JR, Shiro Y, Shibayama N Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7039-44. Epub 2003 May 28. PMID:12773618[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
