Topic: Unnatural amino acids in protein: a biophysical probe to study membrane protein conformation and function

Speaker: Manoj Rana - Michigan State University

Host: Professor Heedeok Hong

Date: Tuesday, November 5, 2019

Time: 4:00 PM

Location: 136 CEM

More Information:

Proteins  carry  out  almost  all  biological processes in our body. This is one reason why solving problems in protein science has been researchers prime interest. In nature, proteins are made up of proteinogenic amino acids; their side chains are unique but are limited to 20 amino acids which also limit protein chemistry. 1
However if we are able to incorporate unnatural amino acids (UAAs) with desired physical, chemical or electronic properties there is no doubt we might be able to incorporate novel properties and function to protein, tailor protein to our advantage and reveal secrets or solve a problem that is otherwise impossible with natural side chains.2 After decades of research, incorporation of UAAs in proteins both in vivo and in vitro is no more a Holy Grail and has been successfully performed by handful of techniques3, it is now an emerging branch in protein engineering and has taken it to a next level.4 In my talk I will discuss about what information can we learn by unnatural amino acids incorporation, how can we incorporate UAAs into protein at desired site and what kind of strategy are necessary for such incorporation? I will also discuss two papers regarding application of UAA incorporation focused on
membrane protein study. In first paper I will discuss how Anap Cyclen-Cu2+ Resonance Energy Transfer (ACCuRET) uses L-Anap (florescent UAA) in FRET pair to visualize conformational changes of soluble and membrane protein.5 In second paper I will discuss how UAAs were used in studying energetics of membrane protein insertion using Flexizyme system(a highly flexible tRNA acylation
method).6 This talk will reveal that stepping beyond 20 natural AAs can grant proteins with novel side chains having unique chemical properties and thereby expands protein chemistry and extends our reach to probe novel physicochemical and biological properties of proteins.

References
1.   Wang et al (2009). Chemistry and Biology. 16(3), 323-336
2.   Liu & Schultz (2010 ). Annu. Rev. Biochem., 79, 413–444
3.    Wals & Ovaa (2014). Front Chem. 2: 15
4.   Zhang et al (2013). Current Opinion in Structural Biology, 23, 581–587
5.   Zagotta et al (2018). eLife,7:e44029
6.   Öjemalm et al (20110. Proc Natl Acad Sci U S A., 108(31), 359-64