Characterization of the β‐chain N‐terminus heterogeneity and the α‐chain C‐terminus of human platelet GPIIb

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Abstract
Human platelet glycoprotein IIb (GPIIb) and IIIa (GPIIIa) form a Ca2+-dependent heterodimer, the integrin GPIIb/IIIa, which functions as the fibrinogen receptor at the surface of activated platelets. GPIIB and GPIIIa are synthesized as single polypeptides from single messages and their amino acid sequences were derived from their cDNAs. The GPIIb precursor is proteolytically processed to yield the known disulphide-bonded two-chain (GPIIbα and GPIIbβ) covalent structure found in mature GPIIb. Our present protein chemical and mass spectrometric analyses indicate that the GPIIb precursor is proteolytically cleaved at two or three sites, to give rise to an homogeneous α-chain (GPIIb 1–856) single disulphidebonded to one of the two β-chains, which are present in a nearly 1:1 ratio: GPIIb β1 (860–1008), with pyroglutamic acid as its blocked N-terminal residue; and GPIIbβ2 (872–1008), with the already known N-terminal sequence. These results satisfy the previously observed electrophoretic size-heterogeneity of the β-chain, confirmed the potential cleavage sites in the junction region, and indicate a probable dual proteolytic processing of GPIIb, which may be relevant to the rest of the two-chain α-subunits of the integrin family.