AHSP Antibodies

Background

AHSP is a small molecule chaperone protein encoded by a specific gene, mainly existing in the red blood cells of vertebrates. This protein maintains the stability and function of hemoglobin by specifically binding to free α-hemoglobin, preventing its oxidation, aggregation and precipitation, and ensuring the normal oxygen transport capacity of red blood cells. During the process of red blood cell differentiation, AHSP is crucial for maintaining the balance of α- and β-hemoglobin chains, and its deficiency may lead to pathological conditions such as hemolytic anemia. This gene was first identified in 2002. Its three-dimensional structure and interaction mechanism were analyzed through X-ray crystallography and other techniques, providing a key molecular basis for the study of hemoglobinopathies and significantly advancing our understanding of protein homeostasis, heme protection and the mechanisms of blood diseases.

Structure Function Application Advantage Our Products

Structure of AHSP

Myoglobin is a relatively small protein with a molecular weight of approximately 16.7 kDa. This weight may slightly vary between species due to minor differences in amino acid sequence.

Species	Human	Mouse	Rhesus monkey	Rat
Molecular Weight (kDa)	10.8	10.7	10.8	10,7
Primary Structural Differences	It contains 3 α -helical domains	90% homology with human source	Highly consistent with the human sequence	With conservative binding interface

This protein is composed of 102 amino acids, and its secondary structure is mainly made up of three α -helices (helices 1-3), which are connected through flexible ring regions to form hydrophobic binding pockets. AHSP specifically binds to free α -hemoglobin through its C-terminal helix. Key residues such as Leu75 and Gln79 play a stabilizing role in the binding interface, effectively preventing the oxidative denaturation and precipitation of α -hemoglobin and maintaining the biological activity of hemoglobin. The three-dimensional structure of AHSP was analyzed by X-ray crystallography, revealing the structural basis of its molecular chaperone mechanism.

Fig. 1:The structure of AHSP. Fig. 1 The structure of AHSP.¹

Key structural properties of AHSP:

Compact triple helix bundle structure
Hydrophobic core surrounded by alpha hemoglobin combined interface
Hydrophobic pockets that specifically bind to free α -hemoglobin

Functions of AHSP

The main function of AHSP is to maintain the stability and solubility of hemoglobin in red blood cells. In addition, it is also involved in a variety of pathophysiological processes, including red blood cell differentiation, oxidative stress response and the mechanism of anemia occurrence.

Function	Description
Stable hemoglobin	Specifically bind to free α -hemoglobin to prevent its denaturation, precipitation and the formation of inclusion bodies.
Protection against oxidative damage	Inhibit the oxidation of heme iron and the generation of free radicals, protecting cells from oxidative stress damage.
Red blood cell maturation support	Promote the correct assembly of α- and β -hemoglobin chains to ensure the normal development of red blood cells.
Adaptation to hypoxia	Maintain hemoglobin function under hypoxic conditions to support the balance of tissue oxygen supply.
Association of disease mechanisms	Abnormal expression of AHSP is closely related to various hemoglobinopathies such as thalassemia.

AHSP functions through the molecular chaperone mechanism, and its binding kinetics shows a high-affinity characteristic, which is different from the synergistic effect of general chaperone proteins, highlighting its unique role in maintaining protein homeostasis within the red blood cell system.

Applications of AHSP and AHSP Antibody in Literature

1. Zurlo, Matteo, et al. "Increased Expression of α-Hemoglobin Stabilizing Protein (AHSP) mRNA in Erythroid Precursor Cells Isolated from β-Thalassemia Patients Treated with Sirolimus (Rapamycin)." Journal of Clinical Medicine 13.9 (2024): 2479. https://doi.org/10.3390/jcm13092479

This study explored the effect of sirolimus (rapamycin) on the expression of α -hemoglobin stabilizing protein (AHSP) in erythroid precursor cells of patients with β -thalassemia. The results showed that the expression of AHSP in patients was higher than that in healthy people and was further induced to increase by sirolimus, suggesting that AHSP could be used as an endpoint indicator in related clinical trials.

2. Mollan, Todd L., et al. "Kinetics of α-globin binding to α-hemoglobin stabilizing protein (AHSP) indicate preferential stabilization of hemichrome folding intermediate." Journal of Biological Chemistry 287.14 (2012): 11338-11350. https://doi.org/10.1074/jbc.m111.313247

The article indicates that AHSP is a molecular chaperone protein that can rapidly bind to and stabilize free α -globin, especially having a higher affinity for the high-iron form (met-α), forming a relatively stable complex, preventing abnormal hemoglobin assembly, and promoting normal hemoglobin production after reduction.

3. Han, Gai, et al. "Nrf2 expands the intracellular pool of the chaperone AHSP in a cellular model of β-thalassemia." Redox biology 50 (2022): 102239. https://doi.org/10.1016/j.redox.2022.102239

The article indicates that AHSP is upregulated in response to excessive α -globin through the Nrf2 pathway in β -thalassemia, which can inhibit α -globin precipitation and ROS production, and improve oxidative stress and protein aggregation during red blood cell differentiation.

4. Walczak, Julia, Maria D. Camargo Johnson, and Kuzhali Muthumalaiappan. "Stage specific expression pattern of alpha-hemoglobin-stabilizing-protein (AHSP) portrayed in erythroblast chronology." Methods and Protocols 3.3 (2020): 46. https://doi.org/10.3390/mps3030046

The article indicates that the expression of AHSP changes dynamically during the maturation of erythroid cells: it is low in the early stage, reaches a peak in the middle stage (8-12 days of culture), and decreases in the late stage, mainly located in the nucleus and excreted along with the nucleus, suggesting that its expression is stage-specific.

5. Dickson, Claire F., et al. "α-Hemoglobin-stabilizing protein (AHSP) perturbs the proximal heme pocket of oxy-α-hemoglobin and weakens the iron-oxygen bond." Journal of Biological Chemistry 288.27 (2013): 19986-20001. https://doi.org/10.1074/jbc.M112.437509

The article indicates that AHSP, as a molecular chaperone, binds to α -hemoglobin (αHb), alters the structure of its heme pockets, stretching the Fe-O₂ bond and promoting O₂ dissociation, thereby accelerating the auto-oxidation of αHb and stabilizing it in an antioxidant state when βHb is insufficient.

Creative Biolabs: AHSP Antibodies for Research

Creative Biolabs specializes in the production of high-quality AHSP antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom AHSP Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our AHSP antibodies, custom preparations, or technical support, contact us at email.

Reference

Mollan, Todd L., et al. "Kinetics of α-globin binding to α-hemoglobin stabilizing protein (AHSP) indicate preferential stabilization of hemichrome folding intermediate." Journal of Biological Chemistry 287.14 (2012): 11338-11350. https://doi.org/10.1074/jbc.m111.313247