2o8e
From Proteopedia
(New page: 200px<br /> <applet load="2o8e" size="450" color="white" frame="true" align="right" spinBox="true" caption="2o8e, resolution 3.300Å" /> '''human MutSalpha (M...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:2o8e.gif|left|200px]]<br /> | + | [[Image:2o8e.gif|left|200px]]<br /><applet load="2o8e" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2o8e" size=" | + | |
caption="2o8e, resolution 3.300Å" /> | caption="2o8e, resolution 3.300Å" /> | ||
'''human MutSalpha (MSH2/MSH6) bound to a G T mispair, with ADP bound to MSH2 only'''<br /> | '''human MutSalpha (MSH2/MSH6) bound to a G T mispair, with ADP bound to MSH2 only'''<br /> | ||
| Line 6: | Line 5: | ||
==Overview== | ==Overview== | ||
Mismatch repair (MMR) ensures the fidelity of DNA replication, initiates, the cellular response to certain classes of DNA damage, and has been, implicated in the generation of immune diversity. Each of these functions, depends on MutSalpha (MSH2*MSH6 heterodimer). Inactivation of this protein, complex is responsible for tumor development in about half of known, hereditary nonpolyposis colorectal cancer kindreds and also occurs in, sporadic tumors in a variety of tissues. Here, we describe a series of, crystal structures of human MutSalpha bound to different DNA substrates, each known to elicit one of the diverse biological responses of the MMR, pathway. All lesions are recognized in a similar manner, indicating that, diversity of MutSalpha-dependent responses to DNA lesions is generated in, events downstream of this lesion recognition step. This study also allows, rigorous mapping of cancer-causing mutations and furthermore suggests, structural pathways for allosteric communication between different regions, within the heterodimer. | Mismatch repair (MMR) ensures the fidelity of DNA replication, initiates, the cellular response to certain classes of DNA damage, and has been, implicated in the generation of immune diversity. Each of these functions, depends on MutSalpha (MSH2*MSH6 heterodimer). Inactivation of this protein, complex is responsible for tumor development in about half of known, hereditary nonpolyposis colorectal cancer kindreds and also occurs in, sporadic tumors in a variety of tissues. Here, we describe a series of, crystal structures of human MutSalpha bound to different DNA substrates, each known to elicit one of the diverse biological responses of the MMR, pathway. All lesions are recognized in a similar manner, indicating that, diversity of MutSalpha-dependent responses to DNA lesions is generated in, events downstream of this lesion recognition step. This study also allows, rigorous mapping of cancer-causing mutations and furthermore suggests, structural pathways for allosteric communication between different regions, within the heterodimer. | ||
| - | |||
| - | ==Disease== | ||
| - | Known diseases associated with this structure: Cafe-au-lait spots, multiple, with leukemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609309 609309]], Cancer susceptibility OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600678 600678]], Colorectal cancer, hereditary nonpolyposis, type 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609309 609309]], Colorectal cancer, hereditary nonpolyposis, type 5 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600678 600678]], Endometrial carcinoma OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600678 600678]], Glioblastoma, early-onset OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609309 609309]], Lymphoma, T-cell OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609309 609309]], Lynch cancer family syndrome II OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609309 609309]], Muir-Torre syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609309 609309]], Neurofibromatosis, type I, with leukemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609309 609309]], Ovarian cancer OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=609309 609309]], Ovarian cancer, endometrial type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600678 600678]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2O8E 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 MG and ADP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2O8E 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=MG:'>MG</scene> and <scene name='pdbligand=ADP:'>ADP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2O8E OCA]. |
==Reference== | ==Reference== | ||
| Line 32: | Line 28: | ||
[[Category: somatic hypermutation]] | [[Category: somatic hypermutation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:01:08 2008'' |
Revision as of 13:01, 23 January 2008
|
human MutSalpha (MSH2/MSH6) bound to a G T mispair, with ADP bound to MSH2 only
Overview
Mismatch repair (MMR) ensures the fidelity of DNA replication, initiates, the cellular response to certain classes of DNA damage, and has been, implicated in the generation of immune diversity. Each of these functions, depends on MutSalpha (MSH2*MSH6 heterodimer). Inactivation of this protein, complex is responsible for tumor development in about half of known, hereditary nonpolyposis colorectal cancer kindreds and also occurs in, sporadic tumors in a variety of tissues. Here, we describe a series of, crystal structures of human MutSalpha bound to different DNA substrates, each known to elicit one of the diverse biological responses of the MMR, pathway. All lesions are recognized in a similar manner, indicating that, diversity of MutSalpha-dependent responses to DNA lesions is generated in, events downstream of this lesion recognition step. This study also allows, rigorous mapping of cancer-causing mutations and furthermore suggests, structural pathways for allosteric communication between different regions, within the heterodimer.
About this Structure
2O8E is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
Structure of the Human MutSalpha DNA Lesion Recognition Complex., Warren JJ, Pohlhaus TJ, Changela A, Iyer RR, Modrich PL, Beese LS, Mol Cell. 2007 May 25;26(4):579-92. PMID:17531815
Page seeded by OCA on Wed Jan 23 15:01:08 2008
