1cka: Difference between revisions
New page: left|200px<br /><applet load="1cka" size="450" color="white" frame="true" align="right" spinBox="true" caption="1cka, resolution 1.50Å" /> '''STRUCTURAL BASIS FOR... |
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[[Image:1cka.jpg|left|200px]]<br /><applet load="1cka" size=" | [[Image:1cka.jpg|left|200px]]<br /><applet load="1cka" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1cka, resolution 1.50Å" /> | caption="1cka, resolution 1.50Å" /> | ||
'''STRUCTURAL BASIS FOR THE SPECIFIC INTERACTION OF LYSINE-CONTAINING PROLINE-RICH PEPTIDES WITH THE N-TERMINAL SH3 DOMAIN OF C-CRK'''<br /> | '''STRUCTURAL BASIS FOR THE SPECIFIC INTERACTION OF LYSINE-CONTAINING PROLINE-RICH PEPTIDES WITH THE N-TERMINAL SH3 DOMAIN OF C-CRK'''<br /> | ||
==Overview== | ==Overview== | ||
BACKGROUND: Proline-rich segments in the guanine nucleotide exchange | BACKGROUND: Proline-rich segments in the guanine nucleotide exchange factor C3G bind much more strongly to the N-terminal Src homology 3 domain (SH3-N) of the proto-oncogene product c-Crk than to other SH3 domains. The presence of a lysine instead of an arginine in the peptides derived from C3G appears to be crucial for this specificity towards c-Crk. RESULTS: In order to understand the chemical basis of this specificity we have determined the crystal structure of Crk SH3-N in complex with a high affinity peptide from C3G (PPPALPPKKR, Kd approximately 2 microM) at 1.5 A resolution. The peptide adopts a polyproline type II helix that binds, as dictated by electrostatic complementarity, in reversed orientation relative to the orientation seen in the earliest structures of SH3-peptide complexes. A lysine in the C3G peptide is tightly coordinated by three acidic residues in the SH3 domain. In contrast, the co-crystal structure of c-Crk SH3-N and a peptide containing an arginine at the equivalent position (determined at 1.9 A resolution) reveals non-optimal geometry for the arginine and increased disorder. CONCLUSIONS: The c-Crk SH3 domain engages in an unusual lysine-specific interaction that is rarely seen in protein structures, and which appears to be a key determinant of its unique ability to bind the C3G peptides with high affinity. | ||
==About this Structure== | ==About this Structure== | ||
1CKA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http:// | 1CKA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CKA OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: complex (oncogene protein/peptide)]] | [[Category: complex (oncogene protein/peptide)]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:06:54 2008'' | ||
Revision as of 10:06, 21 February 2008
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STRUCTURAL BASIS FOR THE SPECIFIC INTERACTION OF LYSINE-CONTAINING PROLINE-RICH PEPTIDES WITH THE N-TERMINAL SH3 DOMAIN OF C-CRK
Overview
BACKGROUND: Proline-rich segments in the guanine nucleotide exchange factor C3G bind much more strongly to the N-terminal Src homology 3 domain (SH3-N) of the proto-oncogene product c-Crk than to other SH3 domains. The presence of a lysine instead of an arginine in the peptides derived from C3G appears to be crucial for this specificity towards c-Crk. RESULTS: In order to understand the chemical basis of this specificity we have determined the crystal structure of Crk SH3-N in complex with a high affinity peptide from C3G (PPPALPPKKR, Kd approximately 2 microM) at 1.5 A resolution. The peptide adopts a polyproline type II helix that binds, as dictated by electrostatic complementarity, in reversed orientation relative to the orientation seen in the earliest structures of SH3-peptide complexes. A lysine in the C3G peptide is tightly coordinated by three acidic residues in the SH3 domain. In contrast, the co-crystal structure of c-Crk SH3-N and a peptide containing an arginine at the equivalent position (determined at 1.9 A resolution) reveals non-optimal geometry for the arginine and increased disorder. CONCLUSIONS: The c-Crk SH3 domain engages in an unusual lysine-specific interaction that is rarely seen in protein structures, and which appears to be a key determinant of its unique ability to bind the C3G peptides with high affinity.
About this Structure
1CKA is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Structural basis for the specific interaction of lysine-containing proline-rich peptides with the N-terminal SH3 domain of c-Crk., Wu X, Knudsen B, Feller SM, Zheng J, Sali A, Cowburn D, Hanafusa H, Kuriyan J, Structure. 1995 Feb 15;3(2):215-26. PMID:7735837
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