Comparison of NMR and crystal structures of membrane proteins and computational refinement to improve model quality

Julia Koehler Leman, Andrew R. D'Avino, Yash Bhatnagar, Jeffrey J Gray

Research output: Contribution to journalArticle

Abstract

Membrane proteins are challenging to study and restraints for structure determination are typically sparse or of low resolution because the membrane environment that surrounds them leads to a variety of experimental challenges. When membrane protein structures are determined by different techniques in different environments, a natural question is “which structure is most biologically relevant?” Towards answering this question, we compiled a dataset of membrane proteins with known structures determined by both solution NMR and X-ray crystallography. By investigating differences between the structures, we found that RMSDs between crystal and NMR structures are below 5 Å in the membrane region, NMR ensembles have a higher convergence in the membrane region, crystal structures typically have a straighter transmembrane region, have higher stereo-chemical correctness, and are more tightly packed. After quantifying these differences, we used high-resolution refinement of the NMR structures to mitigate them, which paves the way for identifying and improving the structural quality of membrane proteins.

Original languageEnglish (US)
Pages (from-to)57-74
Number of pages18
JournalProteins: Structure, Function and Bioinformatics
Volume86
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Membrane Proteins
Crystal structure
Nuclear magnetic resonance
Membranes
X ray crystallography
X Ray Crystallography
Crystals

Keywords

  • membrane proteins
  • protein modeling
  • protein structure
  • Rosetta software
  • structural quality
  • structure refinement

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology

Cite this

Comparison of NMR and crystal structures of membrane proteins and computational refinement to improve model quality. / Koehler Leman, Julia; D'Avino, Andrew R.; Bhatnagar, Yash; Gray, Jeffrey J.

In: Proteins: Structure, Function and Bioinformatics, Vol. 86, No. 1, 01.01.2018, p. 57-74.

Research output: Contribution to journalArticle

@article{87f54dfb245640da8700f32aa682f4d9,
title = "Comparison of NMR and crystal structures of membrane proteins and computational refinement to improve model quality",
abstract = "Membrane proteins are challenging to study and restraints for structure determination are typically sparse or of low resolution because the membrane environment that surrounds them leads to a variety of experimental challenges. When membrane protein structures are determined by different techniques in different environments, a natural question is “which structure is most biologically relevant?” Towards answering this question, we compiled a dataset of membrane proteins with known structures determined by both solution NMR and X-ray crystallography. By investigating differences between the structures, we found that RMSDs between crystal and NMR structures are below 5 {\AA} in the membrane region, NMR ensembles have a higher convergence in the membrane region, crystal structures typically have a straighter transmembrane region, have higher stereo-chemical correctness, and are more tightly packed. After quantifying these differences, we used high-resolution refinement of the NMR structures to mitigate them, which paves the way for identifying and improving the structural quality of membrane proteins.",
keywords = "membrane proteins, protein modeling, protein structure, Rosetta software, structural quality, structure refinement",
author = "{Koehler Leman}, Julia and D'Avino, {Andrew R.} and Yash Bhatnagar and Gray, {Jeffrey J}",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/prot.25402",
language = "English (US)",
volume = "86",
pages = "57--74",
journal = "Proteins: Structure, Function and Genetics",
issn = "0887-3585",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - Comparison of NMR and crystal structures of membrane proteins and computational refinement to improve model quality

AU - Koehler Leman, Julia

AU - D'Avino, Andrew R.

AU - Bhatnagar, Yash

AU - Gray, Jeffrey J

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Membrane proteins are challenging to study and restraints for structure determination are typically sparse or of low resolution because the membrane environment that surrounds them leads to a variety of experimental challenges. When membrane protein structures are determined by different techniques in different environments, a natural question is “which structure is most biologically relevant?” Towards answering this question, we compiled a dataset of membrane proteins with known structures determined by both solution NMR and X-ray crystallography. By investigating differences between the structures, we found that RMSDs between crystal and NMR structures are below 5 Å in the membrane region, NMR ensembles have a higher convergence in the membrane region, crystal structures typically have a straighter transmembrane region, have higher stereo-chemical correctness, and are more tightly packed. After quantifying these differences, we used high-resolution refinement of the NMR structures to mitigate them, which paves the way for identifying and improving the structural quality of membrane proteins.

AB - Membrane proteins are challenging to study and restraints for structure determination are typically sparse or of low resolution because the membrane environment that surrounds them leads to a variety of experimental challenges. When membrane protein structures are determined by different techniques in different environments, a natural question is “which structure is most biologically relevant?” Towards answering this question, we compiled a dataset of membrane proteins with known structures determined by both solution NMR and X-ray crystallography. By investigating differences between the structures, we found that RMSDs between crystal and NMR structures are below 5 Å in the membrane region, NMR ensembles have a higher convergence in the membrane region, crystal structures typically have a straighter transmembrane region, have higher stereo-chemical correctness, and are more tightly packed. After quantifying these differences, we used high-resolution refinement of the NMR structures to mitigate them, which paves the way for identifying and improving the structural quality of membrane proteins.

KW - membrane proteins

KW - protein modeling

KW - protein structure

KW - Rosetta software

KW - structural quality

KW - structure refinement

UR - http://www.scopus.com/inward/record.url?scp=85037971874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85037971874&partnerID=8YFLogxK

U2 - 10.1002/prot.25402

DO - 10.1002/prot.25402

M3 - Article

C2 - 29044728

AN - SCOPUS:85037971874

VL - 86

SP - 57

EP - 74

JO - Proteins: Structure, Function and Genetics

JF - Proteins: Structure, Function and Genetics

SN - 0887-3585

IS - 1

ER -