AGBL-AGBL carboxypeptidase | Elisa - Clia - Antibody - Protein

Background:

GBL (ATP/GTP-binding protein-like) is a family of proteins that includes enzymes with carboxypeptidase activity. These proteins possess ATP/GTP-binding motifs and are structurally related to the ATP-dependent metalloprotease family. AGBL proteins have been implicated in various cellular processes, including protein degradation, post-translational modification, and signal transduction. One specific subgroup within the AGBL family is known for its carboxypeptidase activity. Carboxypeptidases are enzymes that catalyze the hydrolysis of the peptide bond at the carboxy-terminal end of a peptide or protein, releasing a single amino acid. This enzymatic activity plays a crucial role in protein processing and degradation, as well as in the regulation of peptide hormone activity. Dysregulation of AGBL proteins has been implicated in certain diseases, highlighting their importance in cellular homeostasis and pathophysiology.

Protein Structure:

AGBL carboxypeptidases share common structural features:

• ATP/GTP Binding Domain: These enzymes have conserved domains that bind ATP or GTP, which is crucial for their enzymatic activity.
• Carboxypeptidase Domain: This catalytic domain is responsible for the cleavage of peptide bonds, particularly targeting the C-terminal glutamate residues on tubulin.
• Structural Motifs: They contain various motifs that facilitate their interaction with tubulin and possibly other cellular components.

Classification and Subtypes:

The AGBL family consists of several subtypes, each with specific roles and characteristics:

• AGBL1: Involved in the regulation of neuronal microtubules.
• AGBL2: Plays a role in the general regulation of microtubule dynamics.
• AGBL3-5: These members have distinct but overlapping functions in different tissues and cellular processes.

Function and Biological Significance:

AGBL carboxypeptidases are essential for various cellular functions:

• Microtubule Regulation: By removing glutamate residues from tubulin, AGBL enzymes regulate the stability and dynamics of microtubules, which are crucial for cell division, intracellular transport, and cell shape maintenance.
• Cell Signaling: The modification of tubulin can influence signaling pathways that depend on the microtubule network.
• Neuronal Function: AGBL1 and other members are particularly important in neurons, where they contribute to the maintenance and function of the neuronal cytoskeleton.

Interactions:

AGBL carboxypeptidases interact with various proteins and cellular components:

• Tubulin: The primary substrate for AGBL enzymes, tubulin is a major structural component of microtubules.
• Microtubule-Associated Proteins (MAPs): These proteins can modulate the activity of AGBL enzymes and their interaction with microtubules.
• Regulatory Proteins: Proteins involved in cell cycle regulation and intracellular transport may interact with AGBL enzymes to coordinate their activity with cellular needs.

Clinical Issues:

Mutations and dysregulation of AGBL carboxypeptidases are associated with several diseases:

• Neurological Disorders: Given their role in neuronal function, mutations in AGBL genes can lead to neurodegenerative diseases and other neurological conditions.
• Cancer: Altered expression or activity of AGBL enzymes can impact cell division and migration, contributing to tumor development and metastasis.
• Ciliopathies: Since microtubules are a key component of cilia, defects in AGBL enzymes can result in ciliary dysfunction, leading to a range of disorders known as ciliopathies.

Summary:

AGBL carboxypeptidases are crucial enzymes involved in the post-translational modification of tubulin, regulating microtubule dynamics and stability. They play significant roles in various cellular processes, particularly in neurons and during cell division. Interacting with tubulin and other cellular proteins, AGBL enzymes influence key functions such as intracellular transport, cell signaling, and structural integrity. Dysregulation or mutations in AGBL enzymes can lead to neurological disorders, cancer, and ciliopathies, highlighting their importance in maintaining cellular health and function.