1rf0
From Proteopedia
(New page: 200px<br /> <applet load="1rf0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rf0, resolution 2.81Å" /> '''Crystal Structure o...) |
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caption="1rf0, resolution 2.81Å" /> | caption="1rf0, resolution 2.81Å" /> | ||
'''Crystal Structure of Fragment D of gammaE132A Fibrinogen'''<br /> | '''Crystal Structure of Fragment D of gammaE132A Fibrinogen'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1RF0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1RF0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RF0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: recombinant fibrinogen gammae132a]] | [[Category: recombinant fibrinogen gammae132a]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 16:48:24 2008'' |
Revision as of 14:48, 15 February 2008
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Crystal Structure of Fragment D of gammaE132A Fibrinogen
Contents |
Overview
Structural analysis of recombinant fibrinogen fragment D revealed that the, calcium-binding site (beta2-site) composed of residues BbetaAsp261, BbetaAsp398, BbetaGly263, and gammaGlu132 is modulated by the "B:b", interaction. To determine the beta2-site's role in polymerization, we, engineered variant fibrinogen gammaE132A in which calcium binding to the, beta2-site was disrupted by replacing glutamic acid at gamma132 with, alanine. We compared polymerization of gammaE132A to normal fibrinogen as, a function of calcium concentration. Polymerization of gammaE132A at, concentrations of calcium <or=1 mM exhibited an uncharacteristic 2-3-fold, increase in lateral aggregation and fiber thickness compared to normal, fibrinogen, while polymerization of variant and normal were, indistinguishable at 10 mM calcium. These results suggest that the, beta2-site controls the extent of lateral aggregation. That is, when the, calcium anchor (beta2-site) is eliminated before "B:b" interactions occur, then lateral aggregation is enhanced. We solved structures of fragment D, of gammaE132A fibrinogen (rfD-gammaE132A) with and without, Gly-His-Arg-Pro-amide (GHRPam) and found no change to the global, structure. X-ray diffraction data showed GHRPam binding in the "a" and "b", polymerization sites and that calcium could still bind to the beta2-site, of gammaE132A fibrinogen at 70 mM calcium. We found that the gamma2, calcium-binding site (in loop gamma294-301) did not have calcium bound in, the structure of fragment D of gammaE132A fibrinogen with GHRPam bound, (rfD-gammaE132A+GH). Analysis of structures rfD-gammaE132A+GH and, rfD-BbetaD398A+GH indicated that differences in calcium occupation of the, gamma2-site resulted from minor conformational changes provoked by crystal, packing and GHRPam binding to the "a" site did not directly modulate, calcium binding to this site.
Disease
Known diseases associated with this structure: Afibrinogenemia, congenital OMIM:[134820], Afibrinogenemia, congenital OMIM:[134830], Amyloidosis, hereditary renal OMIM:[134820], Dysfibrinogenemia, alpha type, causing bleeding diathesis OMIM:[134820], Dysfibrinogenemia, alpha type, causing recurrent thrombosis OMIM:[134820], Dysfibrinogenemia, beta type OMIM:[134830], Dysfibrinogenemia, gamma type OMIM:[134850], Hypofibrinogenemia, gamma type OMIM:[134850], Thrombophilia, dysfibrinogenemic OMIM:[134830], Thrombophilia, dysfibrinogenemic OMIM:[134850]
About this Structure
1RF0 is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Calcium-binding site beta 2, adjacent to the "b" polymerization site, modulates lateral aggregation of protofibrils during fibrin polymerization., Kostelansky MS, Lounes KC, Ping LF, Dickerson SK, Gorkun OV, Lord ST, Biochemistry. 2004 Mar 9;43(9):2475-83. PMID:14992585
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