Characterizing pathological imperfections in macromolecular crystals: lattice disorders and modulations

Abstract

Macromolecular crystal structure determination can be complicated or brought to a halt by crystal imperfections. These issues motivated us to write up what we affectionately call ‘The Definitive Hitchhiker’s Guide to Pathological Macromolecular Crystals: Lattice Disorders and Modulations’. Perhaps the most challenging imperfections are lattice order–disorder phenomena and positional modulations. Many of these types of crystals have been solved, and progress has been made on the more challenging forms. Diagnostic tools and how to solve many of these problem crystal structures are reviewed. New avenues are provided for approaching the solution of incommensurately modulated crystals. There are a good number of case studies in the literature of lattice order–disorder phenomena and crystallographic modulations that make it timely to write a review. This review concludes with a projected pathway for solving incommensurately modulated crystals, personal views of future directions and needs of the crystallographic community.

KEYWORDS:

• Lattice-translocation defects
• rotational order–disorder
• superlattice
• commensurate
• incommensurate
• translational noncrystallographic symmetry

Acknowledgments

We collaborated with Jason Porta, Clarence Schutt, Uno Lindberg, Kartik Natarajan on these topics over the years. We thank Vaclav Petricek, Garib Murshudov, Sander van Smaalen, Lukas Palatinus, Joe Ferrara, Christer Svensson, Toine Schreurs and Loes Kroon-Batenburg for useful discussion. We thank the University of Nebraska Medical for their support and in particular the Eppley Institute. GB acknowledges the following funding agencies NASA, NSF, Nebraska Research Initiative, NIH, NCI. We also thank all the researchers who persevered and solved their pathological crystal structures.

Disclosure statement

No potential conflict of interest was reported by the authors.

ORCID

Jeffrey J. Lovelace http://orcid.org/0000-0002-4217-8371

Gloria E. O. Borgstahl http://orcid.org/0000-0001-8070-0258

Index

Authors

Campeotto. See NAL

Dauter. See rsTagRFP

Jaskolski. See Hyp-1-ANS

Lohkamp. See CRMP-4

Pearson. See NAL

Pletnev. See rsTagRFP

Read. See Hyp-1-ANS

Rudolph. See FBPase

Turk. See stefin B

Wang. See LEDGF

Bragg, 6, 8, 9

commensurate, 34

Coot. See Software

CRMP-4, 25, 26

CryoEM, 43

DIALS. See Software

Eval15. See Software

FBPase, 29, 30

Hyp-1-ANS, 28, 37

incommensurate, 5, 8, 9, 12, 32, 33, 34, 47

incommensurate diffraction, 33

incommensurate modulation, 5

Jana2006. See Software, See Software

layer translocation defect. See LTD

LEDGF, 21, 22

LTD, 7, 8, 9, 21, 22, 23, 24, 25, 27, 41, 43

MAIN. See Software

Matlab. See Software

Matthew’s Coefficient, 15

modulated structures, 5, 12, 33

MOLREP. See Software

NAL, 41

Order–Disorder, 7, 8, 14, See LTD, See ROD

PA, 8, 10, 35, 36, 41

Patterson map, 9, 10, 21, 23, 27, 29, 30, 43

Perutz, 6

Phaser. See Software

Phenix.refine. See Software

Phenix.xtriage. See Software

Profilin:Actin Complex. See PA

PyMOL. See Software

q-vector, 33, 34, 37, 39, 40, 41

REFMAC5. See Software

ROD, 9, 14, 15, 18, 41, 43

rotational order–disorder, 5, 9, See ROD

rsTagRFP, 9, 15

RStudio. See Software

Satellite reflections, 8, 9, 33, 34, 35, 40, 42

Software

Coot, 13, 17, 18

DIALS, 12

Eval15, 10, 11, 12, 34, 36, 41, 42

Jana2006, 12, 33

MAIN, 13, 18

Matlab, 14

MOLREP, 12, 16, 17

Phaser, 10, 12, 18, 28, 29

Phenix.refine, 13, 17

Phenix.xtriage, 11, 15, 18

PyMOL, 14

REFMAC5, 13, 14, 17, 18, 26

RStudio, 14

Superflip 13, 33 See software

TRUNCATE, 11, 15

Twinsolve, 10, 11, 36

UCLA Twin Detection Server, 11, 15

XPREP, 11, 15

stefin 9, 18, 19, 20

supercell, 10, 32, 34, 36, 37, 39, 40, 41, 42

supercell approximation, 34, 37, 41, 42

superspace, 10, 14, 33, 34, 35, 36, 37, 38, 39, 40

tNCS, 9, 10, 12, 18, 21, 22, 26, 27, 28, 29, 30, 34, 37, 41, 42, 43

translational and rotational non-crystallographic symmetry, 5, See tNCS

Translational non-crystallographic symmetry. See tNCS

translocation layer defects, 5

TRUNCATE. See Software

twinning, 5, 8, 11, 15, 18, 41, 43

Twinsolve. See Software

UCLA Twin Detection Server. See Software

XFEL, 5, 43

XPREP. See Software

Additional information

Funding

This work was supported by National Science Foundation [grant number 1518145].

Notes on contributors

Jeffrey J. Lovelace

Jeffrey J. Lovelace is the x-ray laboratory manager at the Eppley Institute for Research in Cancer and Allied Diseases at the University of Nebraska Medical Center (UNMC) in Omaha, Nebraska in the USA. He received a Bachelor of Science in Engineering Physics from the University of Toledo in 1995. After a brief stint at a small engineering firm prototyping and deploying high-speed inspection equipment for use in various industries, he went back to the University of Toledo on to earn a Master of Science in Bioengineering focusing on Artificial Intelligence in 1998. Then, through a collection of adventures, ended up doing protein crystallography for the purpose of measuring the quality of microgravity grown crystal samples and finally into incommensurate protein crystallography in Gloria Borgstahl’s laboratory at the University of Toledo and at the Eppley Institute in Omaha, NE. He regularly attends the ACA and IUCr meetings as well as the occasional Gordon Conference. His hobbies include golf, snow skiing, shooting trap and skeet, beer and wine tasting but never IPAs.

Gloria E. O. Borgstahl

Gloria E. O. Borgstahl, born the youngest of seven in Dubuque, Iowa, is a Professor in the Eppley Institute for Research in Cancer and Allied Diseases at the University of Nebraska Medical Center (UNMC) in Omaha, Nebraska in the USA. She earned her Bachelor in Science and Engineering degree (B.S.E.) and her Ph.D. in Biochemistry from the University of Iowa in Iowa City, Iowa in 1985 and 1992, respectively. After postdoctoral experiences with Dr. Elizabeth Getzoff and Dr. John Tainer at the Scripps Research Institute in La Jolla, CA and with Dr. Thomas Terwilliger at Los Alamos National Laboratory in Los Alamos, NM, she became an Assistant Professor of Chemistry at the University of Toledo in Toledo, OH. Her research interests in cancer and the structural biology of DNA double-strand break repair brought her to UNMC in 2002. She has regularly attended the Gordon Conference on Diffraction Methods, the IUCr meetings and has been somewhat helpful in the past to the General Interest Group of the ACA. She is currently a member of the Aperiodic Commission for the IUCr. Her main hobbies include anything her children want to do which over the years has included golf, long distance bike riding (RAGBRAI and BRAN in particular), intensely listening and studying music (Led Zepplin, Green Day, Frank Zappa, Red Hot Chili Peppers, and etc.) and its history, Frisbee, our many types of pets and going to international meetings and pretending we live there.