Related Experiment Videos
Amino acid sequence of the alpha subunit of human leukocyte adhesion receptor Mo1 (complement receptor type 3)
M A Arnaout1, S K Gupta, M W Pierce
1Renal Unit, Children's Hospital, Boston, Massachusetts.
Abstract:
Mo1 (complement receptor type 3, CR3; CD11b/CD18) is an adhesion-promoting human leukocyte surface membrane heterodimer (alpha subunit 155 kD [CD11b] noncovalently linked to a beta subunit of 95 kD [CD18]). The complete amino acid sequence deduced from cDNA of the human alpha subunit is reported. The protein consists of 1,136 amino acids with a long amino-terminal extracytoplasmic domain, a 26-amino acid hydrophobic transmembrane segment, and a 19-carboxyl-terminal cytoplasmic domain. The extracytoplasmic region has three putative Ca2+-binding domains with good homology and one with weak homology to the "lock washer" Ca2+-binding consensus sequence. These metal-binding domains explain the divalent cation-dependent functions mediated by Mo1. The alpha subunit is highly homologous to the alpha subunit of leukocyte p150,95 and to a lesser extent, to the alpha subunit of other "integrin" receptors such as fibronectin, vitronectin, and platelet IIb/IIIa receptors in humans and position-specific antigen-2 (PS2) in Drosophila. Mo1 alpha, like p150, contains a unique 187-amino acid stretch NH2-terminal to the metal-binding domains. This region could be involved in some of the specific functions mediated by these leukocyte glycoproteins.
Insights
This study reports the complete amino acid sequence of the Mo1 alpha subunit, a key human leukocyte adhesion molecule. Understanding its structure, including calcium-binding domains, is crucial for elucidating its function in immune responses.
Area of Science:
- Molecular Biology
- Immunology
- Cell Biology
Background:
- Mo1 (complement receptor type 3, CR3; CD11b/CD18) is a critical adhesion molecule on human leukocytes.
- It is a heterodimer composed of alpha (CD11b) and beta (CD18) subunits.
- Its adhesion-promoting function is vital for leukocyte interactions.
Purpose of the Study:
- To determine the complete amino acid sequence of the human Mo1 alpha subunit.
- To analyze the structural domains of the Mo1 alpha subunit.
- To understand the structural basis for Mo1's divalent cation-dependent functions.
Main Methods:
- Deduction of amino acid sequence from complementary DNA (cDNA).
- Bioinformatic analysis of protein domains and homology.
- Comparison with related integrin family members.
Main Results:
- The human Mo1 alpha subunit comprises 1,136 amino acids.
- Key domains identified include an extracytoplasmic region with putative Ca2+-binding sites, a transmembrane segment, and a cytoplasmic tail.
- Significant homology was observed with other integrin alpha subunits, notably leukocyte p150,95.
Conclusions:
- The deduced amino acid sequence provides a foundation for understanding Mo1's structure-function relationships.
- The identified Ca2+-binding domains explain Mo1's divalent cation-dependent activities.
- A unique N-terminal region in Mo1 alpha may contribute to specific leukocyte glycoprotein functions.