التفاصيل البيبلوغرافية
| العنوان: |
Local structural flexibility drives oligomorphism in computationally designed protein assemblies. |
| المؤلفون: |
Khmelinskaia A, Bethel NP, Fatehi F, Antanasijevic A, Borst AJ, Lai SH, Wang JYJ, Mallik BB, Miranda MC, Watkins AM, Ogohara C, Caldwell S, Wu M, Heck AJR, Veesler D, Ward AB, Baker D, Twarock R, King NP |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 Oct 19. Date of Electronic Publication: 2023 Oct 19. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Many naturally occurring protein assemblies have dynamic structures that allow them to perform specialized functions. For example, clathrin coats adopt a wide variety of architectures to adapt to vesicular cargos of various sizes. Although computational methods for designing novel self-assembling proteins have advanced substantially over the past decade, most existing methods focus on designing static structures with high accuracy. Here we characterize the structures of three distinct computationally designed protein assemblies that each form multiple unanticipated architectures, and identify flexibility in specific regions of the subunits of each assembly as the source of structural diversity. Cryo-EM single-particle reconstructions and native mass spectrometry showed that only two distinct architectures were observed in two of the three cases, while we obtained six cryo-EM reconstructions that likely represent a subset of the architectures present in solution in the third case. Structural modeling and molecular dynamics simulations indicated that the surprising observation of a defined range of architectures, instead of non-specific aggregation, can be explained by constrained flexibility within the building blocks. Our results suggest that deliberate use of structural flexibility as a design principle will allow exploration of previously inaccessible structural and functional space in designed protein assemblies. |
| معلومات مُعتمدة: |
U54 AI170856 United States AI NIAID NIH HHS |
| تواريخ الأحداث: |
Date Created: 20231031 Latest Revision: 20240222 |
| رمز التحديث: |
20240222 |
| مُعرف محوري في PubMed: |
PMC10614843 |
| DOI: |
10.1101/2023.10.18.562842 |
| PMID: |
37905007 |
| قاعدة البيانات: |
MEDLINE |
