Metal induced structural changes observed in hexameric insulin
R Sreekanth1, Vasantha Pattabhi, S S Rajan
1Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Chennai, India.
International Journal of Biological Macromolecules
|November 4, 2008
Summary
Metal ions like manganese, rubidium, and nickel influence insulin hexamer structure. Different metal ions induce distinct conformational states, impacting insulin
Area of Science:
- Biochemistry
- Structural Biology
- Protein Chemistry
Background:
- Insulin hexamer structure is regulated by metal ions.
- Conformational transitions (T to R states) are critical for insulin function.
- Understanding metal ion coordination provides insights into insulin stability and activity.
Purpose of the Study:
- To investigate the structural impact of different metal ions (Mn2+, Rb1+, Ni2+) on human arg-insulin.
- To compare the resulting insulin hexamer conformations with the native Zn2+-bound state.
- To elucidate the coordination chemistry of these metal ions within the insulin structure.
Main Methods:
- X-ray crystallography was used to determine the structures of human arg-insulin bound to Mn2+, Rb1+, and Ni2+.
- Comparative analysis of these structures with the known 2Zn2+ human arg-insulin structure.
- Detailed examination of metal ion coordination environments.
Main Results:
- 2Mn2+ and 1Rb1+ human arg-insulin adopted a T3R3f state, similar to 2Zn2+ insulin.
- 4Ni2+ human arg-insulin adopted a T6 conformation.
- Metal coordination was predominantly tetrahedral, except for nickel, which showed dual octahedral and tetrahedral coordination at one site.
- Rubidium selectively occupied a high-affinity metal binding site.
Conclusions:
- The type and coordination of metal ions significantly influence insulin hexamer conformation.
- Distinct metal ions stabilize different structural states (T3R3f vs. T6).
- These findings explain metal-induced structural changes and their implications for insulin.
Related Concept Videos
02:15Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...
02:34Structural Isomerism
Isomerism in Complexes
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can be...
Isomers are different chemical species that have the same chemical formula. Structural isomerism of coordination compounds can be divided into two subcategories, the linkage isomers and coordination-sphere isomers.
Linkage isomers occur when the coordination compound contains a ligand that can bind to the transition metal center through two different atoms. For example, the CN− ligand can bind through the carbon atom or through the nitrogen atom. Similarly, SCN− can be...
01:28Insulin: The Receptor and Signaling Pathways
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but this inhibition is released...
01:25Insulin: Biosynthesis, Chemistry, and Preparation
The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
02:37Metallic Solids
Metallic solids such as crystals of copper, aluminum, and iron are formed by metal atoms. The structure of metallic crystals is often described as a uniform distribution of atomic nuclei within a “sea” of delocalized electrons. The atoms within such a metallic solid are held together by a unique force known as metallic bonding that gives rise to many useful and varied bulk properties.
All metallic solids exhibit high thermal and electrical conductivity, metallic luster, and malleability. Many...
All metallic solids exhibit high thermal and electrical conductivity, metallic luster, and malleability. Many...
02:58Crystal Field Theory - Octahedral Complexes
Crystal Field Theory
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...
To explain the observed behavior of transition metal complexes (such as colors), a model involving electrostatic interactions between the electrons from the ligands and the electrons in the unhybridized d orbitals of the central metal atom has been developed. This electrostatic model is crystal field theory (CFT). It helps to understand, interpret, and predict the colors, magnetic behavior, and some structures of coordination compounds of transition metals.
CFT focuses on...