Jan 1, 1989

Molecular studies of mammalian branched-chain alpha-keto acid dehydrogenase complexes: domain structures, expression, and inborn errors

Annals of the New York Academy of Sciences
D T Chuang

Abstract

We have cloned cDNAs encoding the E1b-alpha, E1b-beta, and E2b subunits of the bovine and human branched-chain alpha-keto acid complexes. The deduced primary structures indicate that the mammalian E2b contains a lipoyl-bearing, an E3-binding, and an inner core domain that are linked in series by two flexible hinge regions. The observed conservation among E2 proteins in each of the three folded domains strongly suggests that the structural cores of alpha-keto acid dehydrogenase complexes are evolutionarily related. We have expressed bovine pre-E2b in E. coli. The lipoate-free precursor protein is enzymatically active and appears to assemble into a 24-mer structure. Studies with deletion mutants support the proposal that the antigenicity in pre-E2b is associated with the flexible proline-rich hinge region. We have observed five distinct molecular phenotypes in maple syrup urine disease (MSUD) cells, according to the pattern of the branched-chain complex protein subunits and mRNAs present. The results have demonstrated a high degree of genetic heterogeneity in MSUD and have identified the affected genes which must be characterized.

Mentioned in this Paper

Inborn Errors of Metabolism
Immunoblotting, Reverse
Alkalescens-Dispar Group
Keto Acids
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Amino Acid Metabolism, Inherited Disorders
Maple Syrup Urine Disease
Complex (molecular entity)
Bos taurus
Lipoate

About this Paper

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Bone Marrow Neoplasms

Bone Marrow Neoplasms are cancers that occur in the bone marrow. Discover the latest research on Bone Marrow Neoplasms here.

IGA Glomerulonephritis

IgA glomerulonephritis is a chronic form of glomerulonephritis characterized by deposits of predominantly Iimmunoglobin A in the mesangial area. Discover the latest research on IgA glomerulonephritis here.

Cryogenic Electron Microscopy

Cryogenic electron microscopy (Cryo-EM) allows the determination of biological macromolecules and their assemblies at a near-atomic resolution. Here is the latest research.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

LRRK2 & Immunity During Infection

Mutations in the LRRK2 gene are a risk-factor for developing Parkinson’s disease. However, LRRK2 has been shown to function as a central regulator of vesicular trafficking, infection, immunity, and inflammation. Here is the latest research on the role of this kinase on immunity during infection.

Antiphospholipid Syndrome

Antiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by the presence of antibodies directed against phospholipids.

Meningococcal Myelitis

Meningococcal myelitis is characterized by inflammation and myelin damage to the meninges and spinal cord. Discover the latest research on meningococcal myelitis here.

Alzheimer's Disease: MS4A

Variants within membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease by recent genome-wide association studies. Here is the latest research.