Sandbox Reserved 1493: Difference between revisions
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The β3 subunit (glycoprotein IIIa) is a 762 amino acids polypeptide chain. | The β3 subunit (glycoprotein IIIa) is a 762 amino acids polypeptide chain. | ||
Its <scene name='80/802667/Beta_head/1'>head</scene> is composed of a '''β I domain''' which has a fold similar to the I domain of the head of the α subunit. | Its <scene name='80/802667/Beta_head/1'>head</scene> is composed of a '''β I domain''' which has a fold similar to the I domain of the head of the α subunit. Is has a <scene name='80/802667/Mg_in_beta_head_midas/2'>Mg2+</scene> coordinating '''metal ion dependent adhesion site (MIDAS)''' motif and a site adjacent to MIDAS ('''ADMIDAS''') which coordinates ions and plays a part in activity modulation. | ||
Its '''stalk''' is mainly composed of a plexin-sempahorin-integrin (PSI) domain and a '''hybrid domain'''. A '''cysteine-rich core''' occupies the extracellular part of β3 from residues 400 to 650. It is linked to the N-terminal of the protein thanks to a long-range disulfide bond. As the globular head is part of the ligand-binding headpiece (1 cation binding site, RGD and KGD binding sites), the cysteine-rich region is thought to have a role in the activation of the headpiece. | Its '''stalk''' is mainly composed of a plexin-sempahorin-integrin (PSI) domain and a '''hybrid domain'''. A '''cysteine-rich core''' occupies the extracellular part of β3 from residues 400 to 650. It is linked to the N-terminal of the protein thanks to a long-range disulfide bond. As the globular head is part of the ligand-binding headpiece (1 cation binding site, RGD and KGD binding sites), the cysteine-rich region is thought to have a role in the activation of the headpiece. | ||
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Multiple '''cation binding sites''' of integrin are located in the head of both subunits and are indirectly involved in ligand binding. <scene name='80/802667/Ca_ions_on_beta-propeller/3'>Calcium ions</scene> in αIIb coordinate '''EF-hand patterns''' (helix-loop-helix calcium binding patterns forming the blades of the β-propeller) which contribute to the structure of the active site and influence ligand binding. | Multiple '''cation binding sites''' of integrin are located in the head of both subunits and are indirectly involved in ligand binding. <scene name='80/802667/Ca_ions_on_beta-propeller/3'>Calcium ions</scene> in αIIb coordinate '''EF-hand patterns''' (helix-loop-helix calcium binding patterns forming the blades of the β-propeller) which contribute to the structure of the active site and influence ligand binding. | ||
The β I domain which also interacts with the ligand includes 3 metal ion binding sites: a <scene name='80/802667/Mg_in_beta_head_midas/ | The β I domain which also interacts with the ligand includes 3 metal ion binding sites: a <scene name='80/802667/Mg_in_beta_head_midas/2'>Mg2+</scene> ion in '''MIDAS''' surrounded by 2 Ca2+ ions (including one from AMIDAS). MIDAS Mg2+ ion coordinates the Asp side chain of ligands containing RGD. | ||
'''AMIDAS''' binds an inhibitory Ca2+ ion and an activating Mn2+ ion resulting in conformational changes. It shows the importance of cation binding sites in '''activity modulation'''. | '''AMIDAS''' binds an inhibitory Ca2+ ion and an activating Mn2+ ion resulting in conformational changes. It shows the importance of cation binding sites in '''activity modulation'''. | ||
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=== KQAGDV binding site === | === KQAGDV binding site === | ||
On stimulated platelets, αIIbβ3 has a highly specific receptor for the plasma protein '''fibrinogen'''. The '''KQAGDV binding site''' interacts with the <scene name='80/802667/Fibrinogen_gamma_c_from_2vdo/ | On stimulated platelets, αIIbβ3 has a highly specific receptor for the plasma protein '''fibrinogen'''. The '''KQAGDV binding site''' interacts with the fibrinogen γ-chain C terminus at the <scene name='80/802667/Fibrinogen_gamma_c_from_2vdo/4'>γHHLGGAKQAGDV sequence</scene> (residues 400 to 411 of γC). <scene name='80/802667/Fibrinogen_gamma_c_kqagd/3'>KQAGD</scene> is the minimal binding motif for αIIbβ3. The <scene name='80/802667/2vdo_asp_mg/3'>Asp side chain interacts with Mg2+</scene> (MIDAS) and the Gly residue enters in a pocket between the two subunits. The peptide of the ligand extends on a large active site on the integrin and has a turn in the backbone that leads the Lys side chain of the KQAGdV sequence into a pocket, so that its ammonium group is involved in hydrogen bonding with the αIIb subunit. | ||
=== RGD binding site === | === RGD binding site === | ||
