scholarly journals Immunodominant-Peptide Recognition: Beta Testing TCRαβ

Immunity ◽  
2008 ◽  
Vol 28 (2) ◽  
pp. 139-141 ◽  
Author(s):  
Jia-huai Wang ◽  
Robert J. Mallis ◽  
Ellis L. Reinherz
2021 ◽  
Vol 433 (13) ◽  
pp. 166992
Author(s):  
Miron Mikhailowitsch Gershkovich ◽  
Victoria Elisabeth Groß ◽  
Oanh Vu ◽  
Clara Tabea Schoeder ◽  
Jens Meiler ◽  
...  

2016 ◽  
Vol 72 (1) ◽  
pp. 168-175 ◽  
Author(s):  
Christian Reichen ◽  
Chaithanya Madhurantakam ◽  
Simon Hansen ◽  
Markus G. Grütter ◽  
Andreas Plückthun ◽  
...  

The armadillo repeat serves as a scaffold for the development of modular peptide-recognition modules. In order to develop such a system, three crystal structures of designed armadillo-repeat proteins with third-generation N-caps (YIII-type), four or five internal repeats (M-type) and second-generation C-caps (AII-type) were determined at 1.8 Å (His-YIIIM4AII), 2.0 Å (His-YIIIM5AII) and 1.95 Å (YIIIM5AII) resolution and compared with those of variants with third-generation C-caps. All constructs are full consensus designs in which the internal repeats have exactly the same sequence, and hence identical conformations of the internal repeats are expected. The N-cap and internal repeats M1to M3are indeed extremely similar, but the comparison reveals structural differences in internal repeats M4and M5and the C-cap. These differences are caused by long-range effects of the C-cap, contacting molecules in the crystal, and the intrinsic design of the repeat. Unfortunately, the rigid-body movement of the C-terminal part impairs the regular arrangement of internal repeats that forms the putative peptide-binding site. The second-generation C-cap improves the packing of buried residues and thereby the stability of the protein. These considerations are useful for future improvements of an armadillo-repeat-based peptide-recognition system.


2018 ◽  
Vol 4 (11) ◽  
pp. eaau1447 ◽  
Author(s):  
Ryan Hard ◽  
Nan Li ◽  
Wei He ◽  
Brian Ross ◽  
Gary C. H. Mo ◽  
...  

Posttranslational modifications (PTMs) play critical roles in regulating protein functions and mediating protein-protein interactions. An important PTM is lysine methylation that orchestrates chromatin modifications and regulates functions of non-histone proteins. Methyllysine peptides are bound by modular domains, of which chromodomains are representative. Here, we conducted the first large-scale study of chromodomains in the human proteome interacting with both histone and non-histone methyllysine peptides. We observed significant degenerate binding between chromodomains and histone peptides, i.e., different histone sites can be recognized by the same set of chromodomains, and different chromodomains can share similar binding profiles to individual histone sites. Such degenerate binding is not dictated by amino acid sequence or PTM motif but rather rooted in the physiochemical properties defined by the PTMs on the histone peptides. This molecular mechanism is confirmed by the accurate prediction of the binding specificity using a computational model that captures the structural and energetic patterns of the domain-peptide interaction. To further illustrate the power and accuracy of our model, we used it to effectively engineer an exceptionally strong H3K9me3-binding chromodomain and to label H3K9me3 in live cells. This study presents a systematic approach to deciphering domain-peptide recognition and reveals a general principle by which histone modifications are interpreted by reader proteins, leading to dynamic regulation of gene expression and other biological processes.


2021 ◽  
Vol 22 (10) ◽  
pp. 1201-1203
Author(s):  
John P. Moore ◽  
Celine R. Gounder
Keyword(s):  

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Silvia C Bobeica ◽  
Shi-Hui Dong ◽  
Liujie Huo ◽  
Nuria Mazo ◽  
Martin I McLaughlin ◽  
...  

The secretion of peptides and proteins is essential for survival and ecological adaptation of bacteria. Dual-functional ATP-binding cassette transporters export antimicrobial or quorum signaling peptides in Gram-positive bacteria. Their substrates contain a leader sequence that is excised by an N-terminal peptidase C39 domain at a double Gly motif. We characterized the protease domain (LahT150) of a transporter from a lanthipeptide biosynthetic operon in Lachnospiraceae and demonstrate that this protease can remove the leader peptide from a diverse set of peptides. The 2.0 Å resolution crystal structure of the protease domain in complex with a covalently bound leader peptide demonstrates the basis for substrate recognition across the entire class of such transporters. The structural data also provide a model for understanding the role of leader peptide recognition in the translocation cycle, and the function of degenerate, non-functional C39-like domains (CLD) in substrate recruitment in toxin exporters in Gram-negative bacteria.


10.2196/15146 ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. e15146 ◽  
Author(s):  
Sara Chew ◽  
Pauline Siew Mei Lai ◽  
Chirk Jenn Ng

Background To date, several medication adherence apps have been developed. However, the existing apps have been developed without involving relevant stakeholders and were not subjected to mobile health app guidelines. In addition, the usability and utility of these apps have not been tested with end users. Objective This study aimed to describe the usability and utility testing of a newly developed medication adherence app—Med Assist—among ambulatory care patients in Malaysia. Methods The Med Assist app was developed based on the Theory of Planned Behavior and the Nielson usability model. Beta testing was conducted from March to May 2016 at a primary care clinic in Kuala Lumpur. Ambulatory care patients who scored ≥40% on the electronic health literacy scale, were aged ≥21 years, and were taking two or more long-term medications were recruited. Two rounds of in-depth interviews were conducted with each participant. The first interview, which was conducted upon participant recruitment, was to assess the usability of Med Assist. Participants were asked to download Med Assist on their phone and perform two tasks (register themselves on Med Assist and enter at least one medication). Participants were encouraged to “concurrently think aloud” when using Med Assist, while nonverbal cues were observed and recorded. The participants were then invited for a second interview (conducted ≥7 days after the first interview) to assess the utility of Med Assist after using the app for 1 week. This was done using “retrospective probing” based on a topic guide developed for utilities that could improve medication adherence. Results Usability and utility testing was performed for the Med Assist app (version P4). A total of 13 participants were recruited (6 men, 7 women) for beta testing. Three themes emerged from the usability testing, while three themes emerged from the utility testing. From the usability testing, participants found Med Assist easy to use and user friendly, as they were able to complete the tasks given to them. However, the details required when adding a new medication were found to be confusing despite displaying information in a hierarchical order. Participants who were caregivers as well as patients found the multiple-user support and pill buddy utility useful. This suggests that Med Assist may improve the medication adherence of patients on multiple long-term medications. Conclusions The usability and utility testing of Med Assist with end users made the app more patient centered in ambulatory care. From the usability testing, the overall design and layout of Med Assist were simple and user friendly enough for participants to navigate through the app and add a new medication. From the participants’ perspectives, Med Assist was a useful and reliable tool with the potential to improve medication adherence. In addition, utilities such as multiple user support and a medication refill reminder encouraged improved medication management.


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