Home
>
Section
>
Chapter
Sen, A.; Hsieh, W.-C.; Aguilar, R.C.
Proceedings of the Ieee. Institute of Electrical and Electronics Engineers 105(2): 385-393
2017
ISSN/ISBN: 0018-9219 PMID: 32963411 DOI:10.1109/jproc.2016.2613076Accession:072664112
Full-Text Article emailed within 0-6 h
Payments are secure & encrypted
Summary
The presence of abnormally expanded glutamine (Q) repeats within specific proteins (e.g., huntingtin) are the well-established cause of several neurogenerative diseases, including Huntington disease and spinocerebellar ataxias. However, the impact of "expanded Q" stretches on the protein function is not well-understood, mostly due to lack of knowledge about the physiological role of Q repeats and the mechanism by which these repeats achieve functional-specificity. Indeed, is intriguing that regions with such low complexity (low information content) can display exquisite functional specificity. Prompting the question: where is this information stored? Applying biochemical/structural constraints and statistical analysis of protein composition we identified Q-rich (QR) regions present in coiled coils of yeast transcription factors and endocytic proteins. Our analysis indicated the existence of non-Q amino-acids differentially enriched or excluded from QR regions in one protein group versus the other. Importantly, when the non-Q amino-acids from an endocytic protein were exchanged by the ones enriched in QR from transcription factors, the resulting protein was unable to localize to the plasma membrane and was instead found in the nucleus. These results indicate that while QR repeats can efficiently engage in binding, the non-Q amino-acids provide essential specificity information. We speculate that coupling low complexity regions with information-intensive determinants might be a strategy used in many protein systems involved in different biological processes.References
Hayashi, Y.; Yamamoto, M.; Seo, H. 1998: Functional analysis of a novel glutamine-rich protein, p86 Environmental Medicine 42(1): 17-19
Roberts, J.D.; Thapaliya, A.; Martínez-Lumbreras, S.; Krysztofinska, E.M.; Isaacson, R.L. 2015: Structural and Functional Insights into Small, Glutamine-Rich, Tetratricopeptide Repeat Protein Alpha Frontiers in Molecular Biosciences 2: 71
Rackovsky, S.; Scheraga, H.A. 2011: On the information content of protein sequences Journal of Biomolecular Structure and Dynamics 28(4): 593
Weiss, O.; Jiménez-Montaño, M.A.; Herzel, H. 2000: Information content of protein sequences Journal of Theoretical Biology 206(3): 379-386
Rooyackers, O.E.; Wagenmakers, A.J.M.; Saris, W.H.M.; Soeters, P.B. 1993: The effect of a dietary protein source rich in glutamine on plasma and muscle concentrations of glutamine in rats Clinical Nutrition 12: 62-63
Wu, T.T.; Fitch, W.M.; Margoliash, E. 1974: The information content of protein amino acid sequences Annual Review of Biochemistry 43(0): 539-566
Lentes, K.U.; Mathieu, E.; Bischoff, R.; Rasmussen, U.B.; Pavirani, A. 1993: Hydrophobic cluster analysis of G protein-coupled receptors: a powerful tool to derive structural and functional information from 2D-representation of protein sequences Journal of Receptor Research 13(1-4): 179-194
Angeletti, P.C.; Walker, D.; Panganiban, A.T. 2002: Small glutamine-rich protein/viral protein U-binding protein is a novel cochaperone that affects heat shock protein 70 activity Cell Stress and Chaperones 7(3): 258-268
Apweiler, R. 2001: Functional information in SWISS-PROT: the basis for large-scale characterisation of protein sequences Briefings in Bioinformatics 2(1): 9-18
Moreau, J.; Marcaud, L.; Maschat, F.; Kejzlarova-Lepesant, J.; Lepesant, J.A.; Scherrer, K. 1982: A + T-rich linkers define functional domains in eukaryotic DNA Nature 295(5846): 260-262
Zukhritdinov, M.N. 1970: Some information on the content of general protein and protein fractions of the blood in relation to the functional state of the thyroid gland in infectious hepatitis Meditsinskii Zhurnal Uzbekistana 2: 58-59
Lemesle-Varloot, L.; Henrissat, B.; Gaboriaud, C.; Bissery, V.; Morgat, A.; Mornon, J.P. 1990: Hydrophobic cluster analysis: procedures to derive structural and functional information from 2-D-representation of protein sequences Biochimie 72(8): 555-574
Perutz, M.F.; Pope, B.J.; Owen, D.; Wanker, E.E.; Scherzinger, E. 2002: Aggregation of proteins with expanded glutamine and alanine repeats of the glutamine-rich and asparagine-rich domains of Sup35 and of the amyloid beta-peptide of amyloid plaques Proceedings of the National Academy of Sciences of the United States of America 99(8): 5596-5600
Ramos, H.; Shannon, P.; Aebersold, R. 2008: The protein information and property explorer: an easy-to-use, rich-client web application for the management and functional analysis of proteomic data Bioinformatics 24(18): 2110-2111
Stryzhova Salova, N.I.; Kutovyi, A.I. 1967: Influence of small doses of ipraside on the functional state of dogs and content of ammonia nitrogen, glutamine, and amide nitrogen in the protein of their brain Ukr Biokhim Zh 39(2): 137-141
Mei, B.G.; Zalkin, H. 1990: Amino-terminal deletions define a glutamine amide transfer domain in glutamine phosphoribosylpyrophosphate amidotransferase and other PurF-type amidotransferases Journal of Bacteriology 172(6): 3512-3514
Weckwerth, W.; Selbig, J. 2003: Scoring and identifying organism-specific functional patterns and putative phosphorylation sites in protein sequences using mutual information Biochemical and Biophysical Research Communications 307(3): 516-521
Boza, J.J.; Maire, J.; Bovetto, L.; Ballèvre, O. 2000: Plasma glutamine response to enteral administration of glutamine in human volunteers (free glutamine versus protein-bound glutamine) Nutrition 16(11-12): 1037-1042
Darmaun, D. 1994: Biodisponibilité de la glutamine et réponse du métabolisme protéique à l'apport de glutamine chez l'homme - Bioavailability of glutamine and effects of glutamine on protein metabolism Nutrition Clinique et Metabolisme (Paris) 8(4): 231-240
Nakashima, H. 2007: Characteristics of human and mouse orthologous protein-coding nucleotide sequences with large g+c content variations Current Genomics 8(7): 445-452
