IBA57 Protein

IBA57 Protein

Introduction

Iba57 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein"> [@guiducci2019]
<table> [@beilschmidt2017]
<tr><th colspan="2">IBA57 Protein</th></tr> [@lill2012]
<tr><td>Protein Name</td><td>Iron-Sulfur Cluster Assembly Factor IBA57</td></tr> [@stehling2014]
<tr><td>Gene</td><td>[IBA57](/genes/iba57)</td></tr> [@senkevich2020]
<tr><td>UniProt</td><td>[Q9H1K0](https://www.uniprot.org/uniprot/Q9H1K0)</td></tr>
<tr><td>Molecular Weight</td><td>40 kDa</td></tr>
<tr><td>Subcellular Localization</td><td>Mitochondria</td></tr>
<tr><td>Protein Family</td><td>Fe-S cluster assembly factor family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

IBA57 (Iron-Sulfur Cluster Assembly Factor) is a mitochondrial protein essential for the maturation of 4Fe-4S cluster-containing proteins. It plays a critical role in iron-sulfur cluster biogenesis, which is fundamental to mitochondrial electron transport chain function and cellular respiration. Mutations in IBA57 cause hereditary spastic paraplegia (SPG74) and severe neurodevelopmental disorders^[1].

Structure

IBA57 Protein

Introduction

Iba57 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein"> [@guiducci2019]
<table> [@beilschmidt2017]
<tr><th colspan="2">IBA57 Protein</th></tr> [@lill2012]
<tr><td>Protein Name</td><td>Iron-Sulfur Cluster Assembly Factor IBA57</td></tr> [@stehling2014]
<tr><td>Gene</td><td>[IBA57](/genes/iba57)</td></tr> [@senkevich2020]
<tr><td>UniProt</td><td>[Q9H1K0](https://www.uniprot.org/uniprot/Q9H1K0)</td></tr>
<tr><td>Molecular Weight</td><td>40 kDa</td></tr>
<tr><td>Subcellular Localization</td><td>Mitochondria</td></tr>
<tr><td>Protein Family</td><td>Fe-S cluster assembly factor family</td></tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>
</div>

Overview

IBA57 (Iron-Sulfur Cluster Assembly Factor) is a mitochondrial protein essential for the maturation of 4Fe-4S cluster-containing proteins. It plays a critical role in iron-sulfur cluster biogenesis, which is fundamental to mitochondrial electron transport chain function and cellular respiration. Mutations in IBA57 cause hereditary spastic paraplegia (SPG74) and severe neurodevelopmental disorders^[1].

Structure

IBA57 contains several key structural features:

• C-terminal Domain: Required for complex formation with ISCA1/ISCA2 proteins
• Fe-S Binding Motifs: Conserved cysteine residues for Fe-S cluster coordination
• Dimerization Interface: Forms functional homodimers in mitochondria

Normal Function

IBA57 is crucial for multiple cellular processes:

Molecular Mechanism

The IBA57-ISCA1-ISCA2 complex operates as a specialized Fe-S cluster assembly module:

• Respiratory chain complexes (NDUFS1, NDUFS2, SDHB)
• DNA repair enzymes (UNG2, SMUG1)
• Metabolic enzymes (aconitase, fumarase)

Role in Disease

Hereditary Spastic Paraplegia (SPG74)

Recessive mutations in IBA57 cause a pure form of hereditary spastic paraplegia with:

• Adult onset (typically 20-40 years)
• Progressive lower limb spasticity
• Mild to moderate paraparesis
• Impaired mitochondrial Fe-S protein maturation in patient fibroblasts^[1]

Multiple Congenital Anomalies-Hypotonia-Seizures (MCAHS)

Severe de novo mutations cause an early-onset disorder characterized by:

• Profound developmental delay
• Seizures
• Dysmorphic features
• Multiple congenital anomalies
• Early childhood mortality due to mitochondrial dysfunction

Neurodegeneration Mechanisms

The link between IBA57 dysfunction and neurodegeneration involves:

Therapeutic Approaches

Currently, no disease-modifying therapies exist for IBA57-related disorders. Potential therapeutic strategies include:

Research Directions

Key research priorities include:

• Understanding the molecular mechanism of 2Fe-2S to 4Fe-4S conversion
• Developing biomarkers for disease progression
• Creating patient-derived cellular models
• Screening for small molecules that enhance IBA57 function

Background

The study of Iba57 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• [IBA57 Gene](/genes/iba57)
• [Hereditary Spastic Paraplegia](/diseases/hereditary-spastic-paraplegia)
• [Mitochondrial Dysfunction Pathway](/mechanisms/mitochondrial-dysfunction)
• [Iron Metabolism](/experiments/astrocyte-ferritin-iron-metabolism-pd)
• Complex I Deficiency
• [Fe-S Cluster Biogenesis](/content/genes)