1hcn: Difference between revisions

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==Overview==

BACKGROUND: Human chorionic gonadotropin (hCG) is a placental hormone that, stimulates secretion of the pregnancy-sustaining steroid progesterone. It, is a member of a family of glycoprotein hormones that are disulfide-rich, heterodimers, with a common alpha-chain and distinctive beta-chains, specific to their particular G-protein linked receptors. RESULTS: We have, produced recombinant hCG in mammalian cells as the selenomethionyl, protein, and have determined its structure (after partial deglycosylation), at 2.6 A resolution from multiwavelength anomalous diffraction (MAD), measurements. Despite only limited sequence similarity (10% identity), the, alpha- and beta-subunits of hCG have similar tertiary folds. Each subunit, has a cystine-knot motif at its core of extended hairpin loops. There is a, very extensive subunit interface featuring two inter-chain beta-sheets and, a unique, disulfide-tethered 'arm' from the beta-subunit which 'embraces', the alpha-subunit. The carboxy-terminal peptide of the beta-subunit, which, is rich in O-linked sugars, is disordered. CONCLUSIONS: Structural and, sequence comparisons indicate an evolutionary homology, albeit remote, between the glycoprotein hormone chains and other cystine-knot proteins, notably platelet-derived growth factor. Segments of the alpha- and, beta-chains that have been convincingly implicated in receptor binding by, hCG are juxtaposed on one side of the molecule. A glycosylation site, implicated in signal transduction but not in binding is also close to the, presumed binding site suggesting a possible coupling between ligand, binding and signaling. This study with selenomethionyl protein produced in, mammalian cells extends the realm of MAD phasing.

BACKGROUND: Human chorionic gonadotropin (hCG) is a placental hormone that stimulates secretion of the pregnancy-sustaining steroid progesterone. It is a member of a family of glycoprotein hormones that are disulfide-rich heterodimers, with a common alpha-chain and distinctive beta-chains specific to their particular G-protein linked receptors. RESULTS: We have produced recombinant hCG in mammalian cells as the selenomethionyl protein, and have determined its structure (after partial deglycosylation) at 2.6 A resolution from multiwavelength anomalous diffraction (MAD) measurements. Despite only limited sequence similarity (10% identity), the alpha- and beta-subunits of hCG have similar tertiary folds. Each subunit has a cystine-knot motif at its core of extended hairpin loops. There is a very extensive subunit interface featuring two inter-chain beta-sheets and a unique, disulfide-tethered 'arm' from the beta-subunit which 'embraces' the alpha-subunit. The carboxy-terminal peptide of the beta-subunit, which is rich in O-linked sugars, is disordered. CONCLUSIONS: Structural and sequence comparisons indicate an evolutionary homology, albeit remote, between the glycoprotein hormone chains and other cystine-knot proteins, notably platelet-derived growth factor. Segments of the alpha- and beta-chains that have been convincingly implicated in receptor binding by hCG are juxtaposed on one side of the molecule. A glycosylation site implicated in signal transduction but not in binding is also close to the presumed binding site suggesting a possible coupling between ligand binding and signaling. This study with selenomethionyl protein produced in mammalian cells extends the realm of MAD phasing.

==About this Structure==

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Structure of human chorionic gonadotropin at 2.6 A resolution from MAD analysis of the selenomethionyl protein., Wu H, Lustbader JW, Liu Y, Canfield RE, Hendrickson WA, Structure. 1994 Jun 15;2(6):545-58. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7922031 7922031]

[[Category: Protein complex]]

[[Category: Canfield, R.E.]]

[[Category: Canfield, R E.]]

[[Category: Hendrickson, W.A.]]

[[Category: Hendrickson, W A.]]

[[Category: Liu, Y.]]

[[Category: Lustbader, J.W.]]

[[Category: Lustbader, J W.]]

[[Category: Wu, H.]]

[[Category: NAG]]

[[Category: hormone]]

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@@ Line 4: / Line 4: @@
 ==Overview==
-BACKGROUND: Human chorionic gonadotropin (hCG) is a placental hormone that, stimulates secretion of the pregnancy-sustaining steroid progesterone. It, is a member of a family of glycoprotein hormones that are disulfide-rich, heterodimers, with a common alpha-chain and distinctive beta-chains, specific to their particular G-protein linked receptors. RESULTS: We have, produced recombinant hCG in mammalian cells as the selenomethionyl, protein, and have determined its structure (after partial deglycosylation), at 2.6 A resolution from multiwavelength anomalous diffraction (MAD), measurements. Despite only limited sequence similarity (10% identity), the, alpha- and beta-subunits of hCG have similar tertiary folds. Each subunit, has a cystine-knot motif at its core of extended hairpin loops. There is a, very extensive subunit interface featuring two inter-chain beta-sheets and, a unique, disulfide-tethered 'arm' from the beta-subunit which 'embraces', the alpha-subunit. The carboxy-terminal peptide of the beta-subunit, which, is rich in O-linked sugars, is disordered. CONCLUSIONS: Structural and, sequence comparisons indicate an evolutionary homology, albeit remote, between the glycoprotein hormone chains and other cystine-knot proteins, notably platelet-derived growth factor. Segments of the alpha- and, beta-chains that have been convincingly implicated in receptor binding by, hCG are juxtaposed on one side of the molecule. A glycosylation site, implicated in signal transduction but not in binding is also close to the, presumed binding site suggesting a possible coupling between ligand, binding and signaling. This study with selenomethionyl protein produced in, mammalian cells extends the realm of MAD phasing.
+BACKGROUND: Human chorionic gonadotropin (hCG) is a placental hormone that stimulates secretion of the pregnancy-sustaining steroid progesterone. It is a member of a family of glycoprotein hormones that are disulfide-rich heterodimers, with a common alpha-chain and distinctive beta-chains specific to their particular G-protein linked receptors. RESULTS: We have produced recombinant hCG in mammalian cells as the selenomethionyl protein, and have determined its structure (after partial deglycosylation) at 2.6 A resolution from multiwavelength anomalous diffraction (MAD) measurements. Despite only limited sequence similarity (10% identity), the alpha- and beta-subunits of hCG have similar tertiary folds. Each subunit has a cystine-knot motif at its core of extended hairpin loops. There is a very extensive subunit interface featuring two inter-chain beta-sheets and a unique, disulfide-tethered 'arm' from the beta-subunit which 'embraces' the alpha-subunit. The carboxy-terminal peptide of the beta-subunit, which is rich in O-linked sugars, is disordered. CONCLUSIONS: Structural and sequence comparisons indicate an evolutionary homology, albeit remote, between the glycoprotein hormone chains and other cystine-knot proteins, notably platelet-derived growth factor. Segments of the alpha- and beta-chains that have been convincingly implicated in receptor binding by hCG are juxtaposed on one side of the molecule. A glycosylation site implicated in signal transduction but not in binding is also close to the presumed binding site suggesting a possible coupling between ligand binding and signaling. This study with selenomethionyl protein produced in mammalian cells extends the realm of MAD phasing.
 ==About this Structure==
@@ Line 12: / Line 12: @@
 Structure of human chorionic gonadotropin at 2.6 A resolution from MAD analysis of the selenomethionyl protein., Wu H, Lustbader JW, Liu Y, Canfield RE, Hendrickson WA, Structure. 1994 Jun 15;2(6):545-58. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7922031 7922031]
 [[Category: Protein complex]]
-[[Category: Canfield, R.E.]]
+[[Category: Canfield, R E.]]
-[[Category: Hendrickson, W.A.]]
+[[Category: Hendrickson, W A.]]
 [[Category: Liu, Y.]]
-[[Category: Lustbader, J.W.]]
+[[Category: Lustbader, J W.]]
 [[Category: Wu, H.]]
 [[Category: NAG]]
 [[Category: hormone]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:55:51 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:59:50 2008''