||The inhibitory cys-loop ligand gated ion channel (LGIC), composed of inhibitory glycine and GABAA receptor, is the major channel to mediate rapid inhibitory nerve transmission in human CNS. Being a member of LGIC, GABAA receptor is the research target of many important therapeutic compounds (e. g., benzodiazepines). All the binding residues in drug binding pocket are allocated on the extracellular (EC) domain at subunit interface. In addition to its pharmacological role, GABAA receptor extracellular domains also carry signal for receptor assembly, specific subunit neighboring interaction and channel gating. For the vast functions involved, the structural information of GABAA extracellular domain becomes valuable, especially in the view of pharmaceutical development. The recent reported X-ray structure of acetylcholine binding protein (AChBP), the EC domain homolog, serves as good starting template for comparative modeling of GABAA receptor EC domain. However, the model remains putative in nature. In the present work, expression studies were carried out in E. coli to achieve soluble expression of three major expressed subunit isoforms(α1, β2 and γ2) of GABAA receptor. All subunits under studies were soluble in fusion of MBP (a chaperone like fusion tag) .All α1, β2 and γ2 subunit fusion protein are biological active, sharing similar secondary structural contents. Mature BZ sensitive GABAA receptor requires proper assembly of α, β and subunits .This assembly process is controlled by signals allocated on the EC domain. In order to achieve large amount of assembled EC domain complex, α1, β2 and γ2 subunits were co-expressed in E. coli for investigation. Coexpression of any subunit combination did not yield any soluble EC domain. However, subunit specific interaction is observed when MBP tagged α1 subunits is used in coexpressing with β2 and γ2 subunits. Conserved tryptophans and cysteine residues are important in structural fold and assembly process in LGIC superfamily. Structural investigation was carried out on EC domain of glycine α1 subunits because it is the simplest when comparison to GABAA receptor. Tyrosine mutation on Trp96, Trp122 and Trp198 revealed that the semi-conserved Trp198 is the most important Trp for tertiary structural maintenance and domain stability. Trp122, the surface solvent exposure tryptophan contributes to global flexibility and regional rigidity of the domain. In addition, conserved cysteine disulfide loop seems to locate proximal to tryptophan residues, and work together to maintain the protein tertiary scaffold.