Sin recombinase crystal structure and dynamics enhance the rotation model /
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| Author / Creator: | Trejo, Caitlin Sullivan, author. |
|---|---|
| Imprint: | 2015. Ann Arbor : ProQuest Dissertations & Theses, 2015 |
| Description: | 1 electronic resource (97 pages) |
| Language: | English |
| Format: | E-Resource Dissertations |
| Local Note: | School code: 0330 |
| URL for this record: | http://pi.lib.uchicago.edu/1001/cat/bib/10773281 |
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| 100 | 1 | |a Trejo, Caitlin Sullivan, |e author. | |
| 245 | 1 | 0 | |a Sin recombinase crystal structure and dynamics enhance the rotation model / |c Trejo, Caitlin Sullivan. |
| 260 | |c 2015. | ||
| 264 | 1 | |a Ann Arbor : |b ProQuest Dissertations & Theses, |c 2015 | |
| 300 | |a 1 electronic resource (97 pages) | ||
| 336 | |a text |b txt |2 rdacontent | ||
| 337 | |a computer |b c |2 rdamedia | ||
| 338 | |a online resource |b cr |2 rdacarrier | ||
| 500 | |a Advisors: Phoebe A. Rice; Ronald S. Rock Committee members: Sean Crosson; Tobin R. Sosnick. | ||
| 502 | |b Ph.D. |c The University of Chicago, Division of the Physical Sciences and Division of the Biological Sciences and Pritzker School of Medicine, Graduate Program in Biophysical Sciences |d 2015. | ||
| 510 | 4 | |a Dissertation Abstracts International, |c Volume: 77-02(E), Section: B. | |
| 520 | |a Sin recombinase is a member of the serine family of site-specific recombinases, which rotate 180° rotation about a relatively flat, hydrophobic protein-protein interface in order to exchange DNA strands. Although rotation is supported by a wealth of biochemical and structural data, previous structures of Sin and of other recombinases showed only one rotational state for any given recombinase, which has hampered modeling of the rotation. In order to better understand the rotational states available to Sin, I solved the crystal structure of the catalytic domains of four new activated mutants of Sin. The asymmetric unit of the crystals of one mutant, Sin I113V, contains three tetramers in two different rotational states. This is the first observation of two rotational states in any serine recombinase. Even across the tetramers that crystallized in a similar rotational state, there was a ∼15° spread in the crossing angles of the E helices. This suggests that favorable packing interfaces observed crystallographically may be more broad and “wiggly” than previously anticipated. I performed normal mode analysis (NMA) on both Sin I113V rotational states and showed that each tetramer’s lowest frequency mode mimics rotation: two protomers rotate as a pair with respect to the other two. However, each tetramer contains a different pivot point. Normal mode analysis also predicts that during rotation, the core of each protomer shifts with respect to the helix that forms the core of the tetramer interface. Taken together, this structural and NMA data suggest that rotation might not be a rigid body movement around a single symmetry axis, as the simplest model of rotation would assume. I propose a more detailed rotation pathway, in which Sin wobbles through 180° of rotation using a combination of pivots at favorable interface packing positions interspersed with hops to new favorable packing positions. This new model provides a basis for further molecular dynamics and single molecule experiments describing rotation by serine recombinases. | ||
| 546 | |a English | ||
| 590 | |a School code: 0330 | ||
| 690 | |a Biophysics. | ||
| 690 | |a Biochemistry. | ||
| 690 | |a Biomechanics. | ||
| 710 | 2 | |a University of Chicago. |e degree granting institution. | |
| 720 | 1 | |a Phoebe A. Rice |e degree supervisor. | |
| 720 | 1 | |a Ronald S. Rock |e degree supervisor. | |
| 856 | 4 | 0 | |u http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3724549 |y ProQuest |
| 929 | |a eresource | ||
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| 928 | |t Library of Congress classification |l Online |c UC-FullText |u http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3724549 |z ProQuest |i 9079508 | ||