Table 1. Reconciling previously... | American Society of Hematology

Table 1.

Reconciling previously described structural features of αIIb and β3 extracellular domains with regions of the αvβ3 crystal structure

Subunit	Old	New	Properties/function
α
	Ca²⁺-binding domain	β-propeller	Known for many years to require μM levels of Ca²⁺ to maintain structural integrity, this 7-bladed, propeller-like domain contributes to the integrin head and forms the major site of contact with the β subunit.
	Heavy-/light-chain cleavage site	NA	Evident only upon reduced SDS-PAGE, posttranslational cleavage of the α subunit takes place within the Golgi apparatus but appears inconsequential for integrin structure or function.
β
	N-terminal cysteine-rich domain	PSI domain	Flexible, immunogenic domain composed of residues 1-54, including 3 disulfide bonds and 1 “extra” cysteine that couples the N-terminus to the bent-hinge region of the integrin; harbors the clinically important Pl^Al alloantigen at Leu₃₃.
	Chymotrypsin-resistant domain	Hybrid domain	Immunoglobulin-like domain composed of discontinuous residues 55-108 and 353-434. The ligand-binding βA domain emerges from the 2 β-sheets that comprise this domain (see below).
	Large disulfide-bonded loop	βA domain	Residues 109-352. The ligand-binding domain that, together with the αIIb β-propeller, forms nearly half of the previously visualized integrin head. Antibodies that bind this domain can inhibit ligand binding; easily removed from the rest of the molecule by protease cleavage at flanking residues 121 and 348. The resulting 66-kDa subunit still contains the Pl^Al epitope but can no longer bind ligand.
	Cysteine-rich repeats	EGF repeats	Protease-resistant stalk composed of 4 repeating EGF domains that may broker integrin conformational changes.

Subunit	Old	New	Properties/function
α
	Ca²⁺-binding domain	β-propeller	Known for many years to require μM levels of Ca²⁺ to maintain structural integrity, this 7-bladed, propeller-like domain contributes to the integrin head and forms the major site of contact with the β subunit.
	Heavy-/light-chain cleavage site	NA	Evident only upon reduced SDS-PAGE, posttranslational cleavage of the α subunit takes place within the Golgi apparatus but appears inconsequential for integrin structure or function.
β
	N-terminal cysteine-rich domain	PSI domain	Flexible, immunogenic domain composed of residues 1-54, including 3 disulfide bonds and 1 “extra” cysteine that couples the N-terminus to the bent-hinge region of the integrin; harbors the clinically important Pl^Al alloantigen at Leu₃₃.
	Chymotrypsin-resistant domain	Hybrid domain	Immunoglobulin-like domain composed of discontinuous residues 55-108 and 353-434. The ligand-binding βA domain emerges from the 2 β-sheets that comprise this domain (see below).
	Large disulfide-bonded loop	βA domain	Residues 109-352. The ligand-binding domain that, together with the αIIb β-propeller, forms nearly half of the previously visualized integrin head. Antibodies that bind this domain can inhibit ligand binding; easily removed from the rest of the molecule by protease cleavage at flanking residues 121 and 348. The resulting 66-kDa subunit still contains the Pl^Al epitope but can no longer bind ligand.
	Cysteine-rich repeats	EGF repeats	Protease-resistant stalk composed of 4 repeating EGF domains that may broker integrin conformational changes.

NA indicates not applicable; and SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis.