Sequential Unfolding of Ankyrin Repeats in Tumor Suppressor p16
The ANK repeat is a ubiquitous 33-residue motif that adopts a β hairpin helix-loop-helix fold. Multiple tandem repeats stack in a linear manner to produce an elongated structure that is stabilized predominantly by short-range interactions between residues close in sequence. The tumor suppressor p16...
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| Veröffentlicht in: | Structure (London) 2003, Vol.11 (1), p.67-73 |
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| creator | Tang, Kit S Fersht, Alan R Itzhaki, Laura S |
| description | The ANK repeat is a ubiquitous 33-residue motif that adopts a β hairpin helix-loop-helix fold. Multiple tandem repeats stack in a linear manner to produce an elongated structure that is stabilized predominantly by short-range interactions between residues close in sequence. The tumor suppressor p16
INK4 consists of four repeats and represents the minimal ANK folding unit. We found from Φ value analysis that p16 unfolded sequentially. The two N-terminal ANK repeats, which are distorted from the canonical ANK structure in all INK4 proteins and which are important for functional specificity, were mainly unstructured in the rate-limiting transition state for folding/unfolding, while the two C-terminal repeats were fully formed. A sequential unfolding mechanism could have implications for the cellular fate of wild-type and cancer-associated mutant p16 proteins. |
| doi_str_mv | 10.1016/S0969-2126(02)00929-2 |
| format | Article |
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INK4 consists of four repeats and represents the minimal ANK folding unit. We found from Φ value analysis that p16 unfolded sequentially. The two N-terminal ANK repeats, which are distorted from the canonical ANK structure in all INK4 proteins and which are important for functional specificity, were mainly unstructured in the rate-limiting transition state for folding/unfolding, while the two C-terminal repeats were fully formed. A sequential unfolding mechanism could have implications for the cellular fate of wild-type and cancer-associated mutant p16 proteins.</description><identifier>ISSN: 0969-2126</identifier><identifier>EISSN: 1878-4186</identifier><identifier>DOI: 10.1016/S0969-2126(02)00929-2</identifier><identifier>PMID: 12517341</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>ankyrin ; Ankyrin Repeat ; Cyclin-Dependent Kinase Inhibitor p16 - chemistry ; Cyclin-Dependent Kinase Inhibitor p16 - metabolism ; Humans ; Models, Molecular ; Mutation ; p16 ; Protein Denaturation ; protein engineering ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; tandem repeat ; Urea - chemistry ; Φ value analysis</subject><ispartof>Structure (London), 2003, Vol.11 (1), p.67-73</ispartof><rights>2003 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-a3dc042208a8836a1b58f2446447f3bf48d6854f856104880fc804ca7ff5471a3</citedby><cites>FETCH-LOGICAL-c505t-a3dc042208a8836a1b58f2446447f3bf48d6854f856104880fc804ca7ff5471a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0969-2126(02)00929-2$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,4024,27923,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12517341$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tang, Kit S</creatorcontrib><creatorcontrib>Fersht, Alan R</creatorcontrib><creatorcontrib>Itzhaki, Laura S</creatorcontrib><title>Sequential Unfolding of Ankyrin Repeats in Tumor Suppressor p16</title><title>Structure (London)</title><addtitle>Structure</addtitle><description>The ANK repeat is a ubiquitous 33-residue motif that adopts a β hairpin helix-loop-helix fold. Multiple tandem repeats stack in a linear manner to produce an elongated structure that is stabilized predominantly by short-range interactions between residues close in sequence. The tumor suppressor p16
INK4 consists of four repeats and represents the minimal ANK folding unit. We found from Φ value analysis that p16 unfolded sequentially. The two N-terminal ANK repeats, which are distorted from the canonical ANK structure in all INK4 proteins and which are important for functional specificity, were mainly unstructured in the rate-limiting transition state for folding/unfolding, while the two C-terminal repeats were fully formed. A sequential unfolding mechanism could have implications for the cellular fate of wild-type and cancer-associated mutant p16 proteins.</description><subject>ankyrin</subject><subject>Ankyrin Repeat</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - chemistry</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</subject><subject>Humans</subject><subject>Models, Molecular</subject><subject>Mutation</subject><subject>p16</subject><subject>Protein Denaturation</subject><subject>protein engineering</subject><subject>Protein Folding</subject><subject>Protein Structure, Secondary</subject><subject>Protein Structure, Tertiary</subject><subject>tandem repeat</subject><subject>Urea - chemistry</subject><subject>Φ value analysis</subject><issn>0969-2126</issn><issn>1878-4186</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkF1LwzAUhoMobk5_gtIr0YvqSZqk6dUYwy8YCG67DlmaSLRra9IK-_dmH-ilV-c98JwPHoQuMdxhwPx-DgUvUoIJvwFyC1CQ2B2hIRa5SCkW_BgNf5EBOgvhAwAIAzhFA0wYzjOKh2g8N1-9qTunqmRZ26YqXf2eNDaZ1J8b7-rkzbRGdSGJcdGvG5_M-7b1JoQYW8zP0YlVVTAXhzpCy8eHxfQ5nb0-vUwns1QzYF2qslIDJQSEEiLjCq-YsIRSTmlus5WlouSCUSsYx0CFAKsFUK1yaxnNscpG6Hq_t_VNfDh0cu2CNlWlatP0QeakYHFb8S8Y_VBeAESQ7UHtmxC8sbL1bq38RmKQW8Vyp1hu_UkgcqdYkjh3dTjQr9am_Js6OI3AeA-Y6OPbGS-DdqbWpnTe6E6WjfvnxA-2L4kP</recordid><startdate>2003</startdate><enddate>2003</enddate><creator>Tang, Kit S</creator><creator>Fersht, Alan R</creator><creator>Itzhaki, Laura S</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><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>7TO</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>2003</creationdate><title>Sequential Unfolding of Ankyrin Repeats in Tumor Suppressor p16</title><author>Tang, Kit S ; Fersht, Alan R ; Itzhaki, Laura S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-a3dc042208a8836a1b58f2446447f3bf48d6854f856104880fc804ca7ff5471a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>ankyrin</topic><topic>Ankyrin Repeat</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - chemistry</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - metabolism</topic><topic>Humans</topic><topic>Models, Molecular</topic><topic>Mutation</topic><topic>p16</topic><topic>Protein Denaturation</topic><topic>protein engineering</topic><topic>Protein Folding</topic><topic>Protein Structure, Secondary</topic><topic>Protein Structure, Tertiary</topic><topic>tandem repeat</topic><topic>Urea - chemistry</topic><topic>Φ value analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tang, Kit S</creatorcontrib><creatorcontrib>Fersht, Alan R</creatorcontrib><creatorcontrib>Itzhaki, Laura S</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Structure (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tang, Kit S</au><au>Fersht, Alan R</au><au>Itzhaki, Laura S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sequential Unfolding of Ankyrin Repeats in Tumor Suppressor p16</atitle><jtitle>Structure (London)</jtitle><addtitle>Structure</addtitle><date>2003</date><risdate>2003</risdate><volume>11</volume><issue>1</issue><spage>67</spage><epage>73</epage><pages>67-73</pages><issn>0969-2126</issn><eissn>1878-4186</eissn><abstract>The ANK repeat is a ubiquitous 33-residue motif that adopts a β hairpin helix-loop-helix fold. Multiple tandem repeats stack in a linear manner to produce an elongated structure that is stabilized predominantly by short-range interactions between residues close in sequence. The tumor suppressor p16
INK4 consists of four repeats and represents the minimal ANK folding unit. We found from Φ value analysis that p16 unfolded sequentially. The two N-terminal ANK repeats, which are distorted from the canonical ANK structure in all INK4 proteins and which are important for functional specificity, were mainly unstructured in the rate-limiting transition state for folding/unfolding, while the two C-terminal repeats were fully formed. A sequential unfolding mechanism could have implications for the cellular fate of wild-type and cancer-associated mutant p16 proteins.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12517341</pmid><doi>10.1016/S0969-2126(02)00929-2</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Access via ScienceDirect (Elsevier); Free Full-Text Journals in Chemistry |
| subjects | ankyrin Ankyrin Repeat Cyclin-Dependent Kinase Inhibitor p16 - chemistry Cyclin-Dependent Kinase Inhibitor p16 - metabolism Humans Models, Molecular Mutation p16 Protein Denaturation protein engineering Protein Folding Protein Structure, Secondary Protein Structure, Tertiary tandem repeat Urea - chemistry Φ value analysis |
| title | Sequential Unfolding of Ankyrin Repeats in Tumor Suppressor p16 |
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