أعرض في EDS

De novo design of buttressed loops for sculpting protein functions.

التفاصيل البيبلوغرافية
العنوان: De novo design of buttressed loops for sculpting protein functions.
المؤلفون: Jiang H; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington., Jude KM; Howard Hughes Medical Institute, Stanford University School of Medicine., Wu K; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington.; Biological Physics, Structure and Design Graduate Program, University of Washington., Fallas J; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington., Ueda G; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington., Brunette TJ; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington., Hicks D; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington., Pyles H; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington., Yang A; Department of Molecular and Cellular Physiology, Stanford University School of Medicine., Carter L; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington., Lamb M; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington., Li X; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington., Levine PM; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington., Stewart L; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington., Garcia KC; Howard Hughes Medical Institute, Stanford University School of Medicine.; Department of Molecular and Cellular Physiology, Stanford University School of Medicine.; Department of Structural Biology, Stanford University School of Medicine., Baker D; Department of Biochemistry, University of Washington.; Institute for Protein Design, University of Washington.; Howard Hughes Medical Institute, Stanford University School of Medicine.; Howard Hughes Medical Institute, University of Washington.
المصدر: BioRxiv : the preprint server for biology [bioRxiv] 2023 Aug 23. Date of Electronic Publication: 2023 Aug 23.
نوع المنشور: Preprint
اللغة: English
بيانات الدورية: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
مستخلص: In natural proteins, structured loops play central roles in molecular recognition, signal transduction and enzyme catalysis. However, because of the intrinsic flexibility and irregularity of loop regions, organizing multiple structured loops at protein functional sites has been very difficult to achieve by de novo protein design. Here we describe a solution to this problem that generates structured loops buttressed by extensive hydrogen bonding interactions with two neighboring loops and with secondary structure elements. We use this approach to design tandem repeat proteins with buttressed loops ranging from 9 to 14 residues in length. Experimental characterization shows the designs are folded and monodisperse, highly soluble, and thermally stable. Crystal structures are in close agreement with the computational design models, with the loops structured and buttressed by their neighbors as designed. We demonstrate the functionality afforded by loop buttressing by designing and characterizing binders for extended peptides in which the loops form one side of an extended binding pocket. The ability to design multiple structured loops should contribute quite generally to efforts to design new protein functions.
التعليقات: Update in: Nat Chem Biol. 2024 Aug;20(8):974-980. doi: 10.1038/s41589-024-01632-2. (PMID: 38816644)
References: Acta Crystallogr D Biol Crystallogr. 2006 Apr;62(Pt 4):439-50. (PMID: 16552146)
Acta Crystallogr D Biol Crystallogr. 2014 May;70(Pt 5):1346-56. (PMID: 24816103)
Acta Crystallogr D Biol Crystallogr. 2010 Jan;66(Pt 1):12-21. (PMID: 20057044)
Acta Crystallogr D Biol Crystallogr. 2008 Jan;64(Pt 1):61-9. (PMID: 18094468)
Nature. 2015 Dec 24;528(7583):580-4. (PMID: 26675729)
Nat Biotechnol. 2023 Aug;41(8):1099-1106. (PMID: 36702895)
Protein Cell. 2018 Jan;9(1):3-14. (PMID: 28271446)
Annu Rev Pharmacol Toxicol. 2015;55:489-511. (PMID: 25562645)
Sci Signal. 2012 May 29;5(226):ra39. (PMID: 22649097)
Science. 2022 Oct 7;378(6615):49-56. (PMID: 36108050)
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877. (PMID: 31588918)
Acta Crystallogr D Biol Crystallogr. 2011 Apr;67(Pt 4):293-302. (PMID: 21460447)
Nat Chem. 2017 Apr;9(4):353-360. (PMID: 28338692)
Nature. 2016 Oct 20;538(7625):329-335. (PMID: 27626386)
J Chem Phys. 2007 Jan 7;126(1):014101. (PMID: 17212484)
J Appl Crystallogr. 2012 Jun 1;45(Pt 3):581-586. (PMID: 22675231)
Nature. 2023 Aug;620(7976):1089-1100. (PMID: 37433327)
Nature. 2022 May;605(7910):551-560. (PMID: 35332283)
BioDrugs. 2020 Aug;34(4):423-433. (PMID: 32583318)
Nat Chem Biol. 2016 Jan;12(1):29-34. (PMID: 26595462)
Proc Natl Acad Sci U S A. 2020 Apr 21;117(16):8870-8875. (PMID: 32245816)
Proc Natl Acad Sci U S A. 2020 Dec 1;117(48):30362-30369. (PMID: 33203677)
Nat Methods. 2024 Jan;21(1):117-121. (PMID: 37996753)
Annu Rev Anal Chem (Palo Alto Calif). 2017 Jun 12;10(1):293-320. (PMID: 28375702)
Bioinformatics. 2010 Mar 1;26(5):689-91. (PMID: 20061306)
Biol Chem. 2019 Feb 25;400(3):275-288. (PMID: 30676995)
Biodes Res. 2022 Oct 10;2022:9842315. (PMID: 37850141)
Methods Enzymol. 2011;487:545-74. (PMID: 21187238)
Nature. 2021 Aug;596(7873):583-589. (PMID: 34265844)
Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16029-34. (PMID: 12461176)
Biopolymers. 1968 Oct;6(10):1425-36. (PMID: 5685102)
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501. (PMID: 20383002)
Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16230-5. (PMID: 17050682)
Nat Methods. 2022 Jan;19(1):11-12. (PMID: 35017726)
Biopolymers. 2008 May;89(5):380-91. (PMID: 18275088)
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):352-67. (PMID: 22505256)
Proc Natl Acad Sci U S A. 2021 Apr 27;118(17):. (PMID: 33879614)
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32. (PMID: 20124692)
Biopolymers. 1983 Dec;22(12):2577-637. (PMID: 6667333)
Nat Methods. 2009 Aug;6(8):606-12. (PMID: 19620974)
Elife. 2013 Sep 10;2:e01456. (PMID: 24040512)
Nat Comput Sci. 2023 May;3(5):382-392. (PMID: 38177840)
Nat Methods. 2013 Jun;10(6):453-4. (PMID: 23624664)
Nat Biotechnol. 2004 May;22(5):575-82. (PMID: 15097997)
Bioinformatics. 2003 Aug 12;19(12):1589-91. (PMID: 12912846)
Nucleic Acids Res. 2005 Apr 22;33(7):2302-9. (PMID: 15849316)
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674. (PMID: 19461840)
Nat Methods. 2020 Jul;17(7):665-680. (PMID: 32483333)
Protein Expr Purif. 2005 May;41(1):207-34. (PMID: 15915565)
Proteins. 2010 Jun;78(8):1950-8. (PMID: 20408171)
معلومات مُعتمدة: P30 GM133894 United States GM NIGMS NIH HHS; P30 GM138396 United States GM NIGMS NIH HHS; S10 OD012289 United States OD NIH HHS
تواريخ الأحداث: Date Created: 20230904 Latest Revision: 20240924
رمز التحديث: 20240924
مُعرف محوري في PubMed: PMC10473674
DOI: 10.1101/2023.08.22.554384
PMID: 37662224
قاعدة البيانات: MEDLINE
الوصف
تدمد:2692-8205
DOI:10.1101/2023.08.22.554384