1hrf: Difference between revisions

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[[Image:1hrf.gif|left|200px]]<br />

[[Image:1hrf.gif|left|200px]]<br /><applet load="1hrf" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1hrf" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1hrf" />

'''SOLUTION STRUCTURE OF THE EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF HEREGULIN-ALPHA, A LIGAND FOR P180ERB4'''<br />

==Overview==

p185erbB-2 and p180erbB-4 are epidermal growth factor (EGF) receptor-like, tyrosine kinases, whose co-expression is observed in many breast, carcinomas. Heregulins (HRGs), which contain an immunoglobulin unit and an, EGF-like domain, bind to p180erbB-4 and activate p180erbB-4 and p185erbB-2, through transphosphorylation or receptor heterodimerization. The EGF-like, domain is sufficient for the activation. Despite the sequence similarity, no cross activity is seen between the p180erbB-4 ligands (HRGs) and the, p170erbB-1 ligands [EGF and transforming growth factor (TGF)-alpha]. To, investigate the structural basis of receptor specificity, we have, determined the solution structure of the EGF-like domain of HRG-alpha by, two-dimensional 1H nuclear magnetic resonance spectroscopy and simulated, annealing calculations. Though its main-chain fold is similar to those of, EGF and TGF-alpha, distinctive structural features are observed on the, molecular surface including an ionic cluster and hydrophobic patches, which afford HRG-alpha the specific affinity for p180erbB-4. The structure, should provide a basis for the structure-activity relationship of HRGs and, for the design of drugs which prevent progression of breast cancer.

p185erbB-2 and p180erbB-4 are epidermal growth factor (EGF) receptor-like tyrosine kinases, whose co-expression is observed in many breast carcinomas. Heregulins (HRGs), which contain an immunoglobulin unit and an EGF-like domain, bind to p180erbB-4 and activate p180erbB-4 and p185erbB-2 through transphosphorylation or receptor heterodimerization. The EGF-like domain is sufficient for the activation. Despite the sequence similarity, no cross activity is seen between the p180erbB-4 ligands (HRGs) and the p170erbB-1 ligands [EGF and transforming growth factor (TGF)-alpha]. To investigate the structural basis of receptor specificity, we have determined the solution structure of the EGF-like domain of HRG-alpha by two-dimensional 1H nuclear magnetic resonance spectroscopy and simulated annealing calculations. Though its main-chain fold is similar to those of EGF and TGF-alpha, distinctive structural features are observed on the molecular surface including an ionic cluster and hydrophobic patches, which afford HRG-alpha the specific affinity for p180erbB-4. The structure should provide a basis for the structure-activity relationship of HRGs and for the design of drugs which prevent progression of breast cancer.

==Disease==

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==About this Structure==

1HRF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://~~ispc~~.weizmann.ac.il/oca-bin/ocashort?id=1HRF OCA].

1HRF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HRF OCA].

==Reference==

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[[Category: growth factor]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 17~~:21:~~26 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:04:05 2008''

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-[[Image:1hrf.gif|left|200px]]<br />
+[[Image:1hrf.gif|left|200px]]<br /><applet load="1hrf" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1hrf" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1hrf" />
 '''SOLUTION STRUCTURE OF THE EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF HEREGULIN-ALPHA, A LIGAND FOR P180ERB4'''<br />
 ==Overview==
-p185erbB-2 and p180erbB-4 are epidermal growth factor (EGF) receptor-like, tyrosine kinases, whose co-expression is observed in many breast, carcinomas. Heregulins (HRGs), which contain an immunoglobulin unit and an, EGF-like domain, bind to p180erbB-4 and activate p180erbB-4 and p185erbB-2, through transphosphorylation or receptor heterodimerization. The EGF-like, domain is sufficient for the activation. Despite the sequence similarity, no cross activity is seen between the p180erbB-4 ligands (HRGs) and the, p170erbB-1 ligands [EGF and transforming growth factor (TGF)-alpha]. To, investigate the structural basis of receptor specificity, we have, determined the solution structure of the EGF-like domain of HRG-alpha by, two-dimensional 1H nuclear magnetic resonance spectroscopy and simulated, annealing calculations. Though its main-chain fold is similar to those of, EGF and TGF-alpha, distinctive structural features are observed on the, molecular surface including an ionic cluster and hydrophobic patches, which afford HRG-alpha the specific affinity for p180erbB-4. The structure, should provide a basis for the structure-activity relationship of HRGs and, for the design of drugs which prevent progression of breast cancer.
+p185erbB-2 and p180erbB-4 are epidermal growth factor (EGF) receptor-like tyrosine kinases, whose co-expression is observed in many breast carcinomas. Heregulins (HRGs), which contain an immunoglobulin unit and an EGF-like domain, bind to p180erbB-4 and activate p180erbB-4 and p185erbB-2 through transphosphorylation or receptor heterodimerization. The EGF-like domain is sufficient for the activation. Despite the sequence similarity, no cross activity is seen between the p180erbB-4 ligands (HRGs) and the p170erbB-1 ligands [EGF and transforming growth factor (TGF)-alpha]. To investigate the structural basis of receptor specificity, we have determined the solution structure of the EGF-like domain of HRG-alpha by two-dimensional 1H nuclear magnetic resonance spectroscopy and simulated annealing calculations. Though its main-chain fold is similar to those of EGF and TGF-alpha, distinctive structural features are observed on the molecular surface including an ionic cluster and hydrophobic patches, which afford HRG-alpha the specific affinity for p180erbB-4. The structure should provide a basis for the structure-activity relationship of HRGs and for the design of drugs which prevent progression of breast cancer.
 ==Disease==
@@ Line 11: / Line 10: @@
 ==About this Structure==
-HRF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HRF OCA].
+HRF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HRF OCA].
 ==Reference==
@@ Line 24: / Line 23: @@
 [[Category: growth factor]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:21:26 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:04:05 2008''