View this email in your browser

December 2022

President's Column

Under the Microscope:
The Island of Misfit Toys

My first encounter with the heroic epic genre was in 1966 when I saw “Rudolph the Red-Nosed Reindeer,” the hour-long stop-motion movie produced by Jules Bass and Arthur Rankin. This film is shown, without fail, on network TV every December. Even on black and white TV, the Abominable Snowman is absolutely terrifying to a 5 year old. Rare is the year since then that I have not watched this charming film. Indeed, I stumbled onto it just a week ago…

As in The Odyssey and The Aeneid, the Rankin/Bass Rudolph epic is narrated by a detached third-party (i.e., Sam the Snowman) who draws in the viewer with a proem (a formal preface). Sam’s proem closely resembles a classical invocation of the muses. There is, of course, a heroic quest: Rudolph and his friend Hermey (an elf and would-be dentist) are banished from North Pole society and journey into the great white void in search of self-realization. They have a series of adventures, including a foray into the underworld (the cave of the Abominable Snowman) and an encounter with death (a seemingly unsurvivable fall from a precipice). They face dangers but also make unforeseen friends—most notably the prospector Yukon Cornelius and his sled team of pet-looking dogs. Ultimately, bright Rudolph and clever Hermey achieve their quest, using their perceived inadequacies to triumph over their enemies and former detractors. As in many other epics, the Reindeer saga even includes an enumeratio in which Sam lists the names of all the reindeer who comprise the flying-sleigh-team.

One of the stops on Rudolph and Hermey’s quest is the Island of Misfit Toys, a sort of orphanage for unwanted toys with unconventional features such as a square-wheeled train and a water pistol that squirts jelly. Being misfits themselves, Rudolph and Hermey request permission from the stern but kindly King Moonracer to dwell on the isle. They are allowed to spend the night, but the King explains that—as living creatures—it is not appropriate for them to live among the toys. Yukon observes: “Even among misfits you’re misfits!” It all works out in the end when Rudolph returns to the Island with his blizzard-defying beacon as the head of the flying reindeer that will pick up toys and deliver them to children with eclectic taste.

The Island of Misfit Toys has been on my mind a lot lately. This is partly because the membrane proteins we study don’t behave the way well-bred proteins ought to behave. They are misfits and a source of endless vexation. It is also so easy as a protein scientist to personally identify with the trials and tribulations of misfits. Scientists at all career stages encounter faculty who give us a rough time at meetings, cells that will not grow, editors that tell us our work is unworthy of review, an endless series of new and un-funded regulatory requirements, unsympathetic reviewers, and many other challenges and setbacks. We’re all misfits!

Nevertheless, there is a lot to be said for being misfits. There is a glory to our sometimes scruffy careers. Being a scientist may not always be a bed of roses, but we certainly are having fun. While most of the low-hanging fruit projects were polished off long ago, the fact that all the good projects are now Island of Misfit Toys material is exactly what make them so interesting.

One of the most touching features in the Reindeer epic is when Rudolph’s mother, along with his girlfriend Clarice, bravely depart the North Pole into the barren waste to search for Rudolph and Hermey, only to themselves be ensnared by the Abominable. Without hesitation, Rudolph and his friends risk all and combine their talents to rescue them from a cruel fate. It’s all so moving that even the cold heart of the Abominable is melted. I hope that we will all look out for each other in the very same way. To quote Hermey when he and Rudolph first met: “Let’s be misfits together!”

Happy Holidays from The Protein Society!

I thank Shannan Cunniffe, Wade Van Horn, Becky Sanders, and Raluca Cadar for their edits and helpful comments. It is noted that Jules Bass passed away on Oct. 25, 2022. For any other Rudolph geeks out there, check out this later-cut scene from the original 1964 version. It provides a satisfying resolution to the prospecting aspirations of Mr. Cornelius.

PS37 Preliminary Sessions

Session 1: Modern Anti-viral Strategies

Peijun Zhang, Diamond Light Source
Christopher Barnes, Stanford University
Celia Schiffer, University of Massachusetts Chan Medical School

Session 2: Protein Folding and Function in Context

Patricia Clark, University of Notre Dame
Bil Clemons, California Institute of Technology
Christian Kaiser, Johns Hopkins University

Session 3: Structures of Mega-Complexes

Alan Brown, Harvard University
Andre Hoelz, California Institute of Technology
Eva Nogales, University of California, Berkeley

Session 4: Protein Evolution: Lessons from the Past

Betul Kacar, University of Wisconsin-Madison
Shelley Copley, University of Colorado, Boulder
Jose Sanchez-Ruiz, Universidad de Granada

Session 5: RNA-Protein Machines: Ancient Synergies

Jingyi Fei, University of Chicago
Aaron Hoskins, University of Wisconsin-Madison
Rachel Green, Johns Hopkins University

Session 6: Peptide Modalities: Size Doesn't Matter

Christina Schroeder, Genentech
Cameron Pye, Unnatural Products
Lauren Monovich, Novartis Institutes for BioMedical Research

Session 7: Capturing Protein Interactions

James Munro, University of Massachusetts Chan Medical School
Giulia Palermo, University of California Riverside
Neel Shah, Columbia University

Session 8: Membrane Proteins: From Natural to Designed

Tae-Young Yoon, Seoul National University
William DeGrado, University of California, San Francisco
Nieng Yan, Princeton University
Shuguang Zhang, Massachusetts Institute of Technology

Session 9: Structure Prediction and Design

Eva Maria Strauch, University of Georgia
Kresten Lindorff-Larsen, University of Copenhagen

Session 10: Proteins in Motion

Jane Dyson, Scripps Research Institute
Rodrigo Maillard, Georgetown University
David Rueda, Imperial College London

Session 11: Engineering Protein Fate and Function

Ray Deshaies, Amgen
Dan Nomura, University of California, Berkeley
Sara Buhrlage, Harvard University

Session 12: Aggregates, Amyloids, or Condensates?

Ibrahim Cisse, Massachusetts Institute of Technology
Rohit Pappum, Washington University in St. Louis
Amy Gladfelter, University of North Carolina at Chapel Hill

Protein Science Journal
December 2022

From the desk of Jeanine Amacher, Ph.D.
This issue includes 21 Full-Length, 3 Methods and Applications, and 10 Tools for Protein Science papers, as well as 1 Review. The Review discusses and evolutionary history of the Co-A binding protein Nat/Ivy (Longo LM, Hirai H, and Mcglynn SE). The Tools for Protein Science papers describe: (1) an invited Tools issue contribution on the RCSB Protein Data bank, now in its 52nd year (Burley SK, et al.), (2) a resource (Dockground) that provides a collection of datasets for “the development and testing of protein docking techniques” (Collins KW, et al.), (3) a web server (BindWeb) for ligand binding residue and pocket prediction from protein structures (Xia Y, et al.), (4) an electron tomography toolbox (ArtiaX) for the interactive handling of sub-tomograms in UCSF ChimeraX (Ermel UH, et al.), and many others. The Materials and Applications papers include: (1) a protocol for purifying a model protein, HtrA, from inclusion bodies under denaturing conditions using a high-throughput screen for optimal refolding buffer composition (Ronzetti M, et al.), (2) using inline small-angle X-ray scattering-coupled chromatography under high pressure (Miller RC, et al.), and (3) a study using a deep neural network model (DeepET) to “provide a temperature-related statistical summary of protein sequences and capture structural properties that affect thermal stability” in over 3 million enzymes from the BRENDA enzyme database (Li G and Buric L, et al.).

In this issue, there are 21 Full-Length papers. Some highlights include: (1) an investigation of mutated or truncated variants of the intermembrane human Na+/H+ antiporter NHA2 (Velazquez D, et al.), (2) characterization of ancestral PrP proteins to study the origin of infectious misfolding prion disease (Cortez LM, et al.), (3) the use of phage display to select and subsequently characterize a programmed cell death protein 1 (PD-1) blocking antibody (Peissert F, Pluss L, Giudice AM, et al.), (4) a paper dissecting the individual peptide exchange steps that occur at low pH for major histocompatibility complex class I (MHC-I) proteins (Saikia A, et al.), (5) an investigation of the gelation of heat-soluble proteins from tardigrades, which may prove effective protective molecules for protein-based pharmaceuticals (Eicher JE, et al.), (6) the structural and biochemical characterization of a PET hydroylase, PET6, from Vibrio gazogenes (Weigart S, et al.), (7) the design of a H2O2 self-producing P450SPalpha enzyme, which may be a good candidate as an industrial biocatalyst (Giuriato D, et al.), (8) the phage-assisted, active site-directed ligand evolution (PADLE) of a histone deacetylase 8 inhibitor (Morse JS, et al.), and (9) a paper defining the structural changes of urea-induced unfolding of an ankyrin repeat protein at atomic resolution (Sudharsan Medur Gurushankar M, Dalvi S, and Venkatraman P).

If you are an early career scientist, the Protein Science Early Career Reviewer board would love to include you! Please send a current CV and 5-10 research keywords to amacher.proteinscience@gmail.com. Postdoctoral fellows are also encouraged to apply, but we are asking you to additionally have 2 letters of recommendation submitted on your behalf.

TPS members benefit from reduced rates to publish in the journal, and free access to the journal.

Register today for our next webinar, set for January 24, 2023 from 10 a.m. - Noon EST.

We're Moving!

TPS staff has been working behind the scenes to migrate our current website to a new platform. Our fresh new site will allow us to utilize features that will improve our members and constituents' experiences. As is typical with many upgrades, it will require all users to create a new account (and our least favorite request of the century - set up a new password). Don't worry, we will share more information as the migration draws closer, but expect it to be up and in January.

Call For Webinars
We are inviting proposals for 2023 Protein Society Webinars. Webinars are 2 hours long and include four speakers and an organizer/facilitator (who can also be one of the four speakers). If you would like to organize a webinar, please message us with (1) suggested webinar topic, (2) three proposed speakers, and (3) suggested month(s) (if you have preferences). If your webinar is approved, we will work with you to choose a series of possible dates and times, at which point you will invite the speakers and work with them to pick the final date and time. The Society will then advertise, set up, and host the webinar. This is a great opportunity for you to bring cool protein science research to the attention of our community!

Share Your Stories

Members - are you celebrating a recent achievement in protein science? Have exciting research news? Submit to our monthly newsletter. Please send news of your award, a photo, and a press release if available. Additionally, let us know of upcoming meetings, conferences, or workshops TPS members would be interested in attending.

Contact us.