This work reports the structural and functional characterization of the platelet glycoprotein complex GPIIb-IIIa (integrin alpha IIb beta 3) in a patient of type II Glanzmann thrombasthenia, bearing a homozygous G-->A base transition at position 1074 of GPIIb that results in an Arg327-->His substitution. CHO cells stably transfected with cDNA encoding His327GPIIb showed a drastic reduction in the surface expression of alpha IIb beta 3 complex relative to control cells transfected with wild type GPIIb. Immunoprecipitation analysis demonstrated that GPIIb synthesis, heterodimerization, and short term maturation were not impeded, suggesting that conformational changes dependent on Arg327 of GPIIb may play an essential role in either the rate of maturation and/or transport of heterodimers to the cell surface. Cotransfection of CHO cells with equimolar amounts of cDNAs encoding wild type and mutant His327-GPIIb led to a marked reduction in the surface expression of alpha IIb beta 3. This novel observation of a dominant-negative effect of the mutant His 327 alpha IIb subunit provides a molecular basis for the reduced platelet alpha IIb beta 3 content observed in the heterozygous offspring.