The MDMX Acidic Domain Uses Allovalency to Bind Both p53 and MDMX
Autoinhibition of p53 binding to MDMX requires two short-linear motifs (SLiMs) containing adjacent tryptophan (WW) and tryptophan-phenylalanine (WF) residues. NMR spectroscopy was used to show the WW and WF motifs directly compete for the p53 binding site on MDMX and circular dichroism spectroscopy...
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| Veröffentlicht in: | Journal of molecular biology 2022-11, Vol.434 (22), p.167844-167844, Article 167844 |
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| container_end_page | 167844 |
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| container_issue | 22 |
| container_start_page | 167844 |
| container_title | Journal of molecular biology |
| container_volume | 434 |
| creator | Fenton, Malissa Borcherds, Wade Chen, Lihong Anbanandam, Asokan Levy, Robin Chen, Jiandong Daughdrill, Gary |
| description | Autoinhibition of p53 binding to MDMX requires two short-linear motifs (SLiMs) containing adjacent tryptophan (WW) and tryptophan-phenylalanine (WF) residues. NMR spectroscopy was used to show the WW and WF motifs directly compete for the p53 binding site on MDMX and circular dichroism spectroscopy was used to show the WW motif becomes helical when it is bound to the p53 binding domain (p53BD) of MDMX. Binding studies using isothermal titration calorimetry showed the WW motif is a stronger inhibitor of p53 binding than the WF motif when they are both tethered to p53BD by the natural disordered linker. We also investigated how the WW and WF motifs interact with the DNA binding domain (DBD) of p53. Both motifs bind independently to similar sites on DBD that overlap the DNA binding site. Taken together our work defines a model for complex formation between MDMX and p53 where a pair of disordered SLiMs bind overlapping sites on both proteins. |
| doi_str_mv | 10.1016/j.jmb.2022.167844 |
| format | Article |
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Taken together our work defines a model for complex formation between MDMX and p53 where a pair of disordered SLiMs bind overlapping sites on both proteins.</description><subject>Amino Acid Motifs</subject><subject>Humans</subject><subject>Phenylalanine - chemistry</subject><subject>Protein Binding</subject><subject>Protein Domains</subject><subject>Proto-Oncogene Proteins c-mdm2 - chemistry</subject><subject>Tryptophan - chemistry</subject><subject>Tumor Suppressor Protein p53 - chemistry</subject><issn>0022-2836</issn><issn>1089-8638</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEtPwzAQhC0EoqXwA7ggH7mkrGPXjwtSaHlJrbi0EjfLcRyaKolLnFbqvydVSwWn1WpnZkcfQrcEhgQIf1gNV1U6jCGOh4QLydgZ6hOQKpKcynPUh-4SxZLyHroKYQUAI8rkJepRTiQRgvVRMl86PJvMPnFii6yweOIrU9R4EVzASVn6rSldbXe49fipqDP85NslXo8oNt2yN16ji9yUwd0c5wAtXp7n47do-vH6Pk6mkaVKtZGTVI0gNVQKmtrMElBGQcZyiKmyzjmTqxRylbu8KyeMZSyjhlvgigsBgg7Q4yF3vUkrl1lXt40p9bopKtPstDeF_n-pi6X-8lutOGOS0i7g_hjQ-O-NC62uimBdWZra-U3QsYiBxUop3knJQWobH0Lj8tMbAnqPXq90h17v0esD-s5z97ffyfHLmv4ADlV-zw</recordid><startdate>20221130</startdate><enddate>20221130</enddate><creator>Fenton, Malissa</creator><creator>Borcherds, Wade</creator><creator>Chen, Lihong</creator><creator>Anbanandam, Asokan</creator><creator>Levy, Robin</creator><creator>Chen, Jiandong</creator><creator>Daughdrill, Gary</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3459-4014</orcidid><orcidid>https://orcid.org/0000-0001-5655-6559</orcidid></search><sort><creationdate>20221130</creationdate><title>The MDMX Acidic Domain Uses Allovalency to Bind Both p53 and MDMX</title><author>Fenton, Malissa ; Borcherds, Wade ; Chen, Lihong ; Anbanandam, Asokan ; Levy, Robin ; Chen, Jiandong ; Daughdrill, Gary</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-e83950ba3873bcdc109a90d4f0239ceeeaf9b0f9fef6187ac44d3a6c069677073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Amino Acid Motifs</topic><topic>Humans</topic><topic>Phenylalanine - chemistry</topic><topic>Protein Binding</topic><topic>Protein Domains</topic><topic>Proto-Oncogene Proteins c-mdm2 - chemistry</topic><topic>Tryptophan - chemistry</topic><topic>Tumor Suppressor Protein p53 - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fenton, Malissa</creatorcontrib><creatorcontrib>Borcherds, Wade</creatorcontrib><creatorcontrib>Chen, Lihong</creatorcontrib><creatorcontrib>Anbanandam, Asokan</creatorcontrib><creatorcontrib>Levy, Robin</creatorcontrib><creatorcontrib>Chen, Jiandong</creatorcontrib><creatorcontrib>Daughdrill, Gary</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fenton, Malissa</au><au>Borcherds, Wade</au><au>Chen, Lihong</au><au>Anbanandam, Asokan</au><au>Levy, Robin</au><au>Chen, Jiandong</au><au>Daughdrill, Gary</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The MDMX Acidic Domain Uses Allovalency to Bind Both p53 and MDMX</atitle><jtitle>Journal of molecular biology</jtitle><addtitle>J Mol Biol</addtitle><date>2022-11-30</date><risdate>2022</risdate><volume>434</volume><issue>22</issue><spage>167844</spage><epage>167844</epage><pages>167844-167844</pages><artnum>167844</artnum><issn>0022-2836</issn><eissn>1089-8638</eissn><abstract>Autoinhibition of p53 binding to MDMX requires two short-linear motifs (SLiMs) containing adjacent tryptophan (WW) and tryptophan-phenylalanine (WF) residues. 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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Amino Acid Motifs Humans Phenylalanine - chemistry Protein Binding Protein Domains Proto-Oncogene Proteins c-mdm2 - chemistry Tryptophan - chemistry Tumor Suppressor Protein p53 - chemistry |
| title | The MDMX Acidic Domain Uses Allovalency to Bind Both p53 and MDMX |
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