WALP peptides are a class of synthesized, membrane-spanning α-helices composed of tryptophan (W), alanine (A), and leucine (L) amino acids. They are designed to study properties of proteins in lipid membranes such as orientation, extent of insertion, and hydrophobic mismatch.[1]
WALP-19 protein peptide of the following sequence of 19 amino acids: GWWLALALALALALALWWA. Tryptophan residues are shown in green while leucines and alanines are displayed in red and blue, respectively.
Significanceedit
The transmembrane region of many integral membrane proteins consists of one or more alpha helices. The orientations and interactions of these helices directly affect cell signaling and molecular transport across the bilayer. The hydrophobic environment of the phospholipid tails in turn modulates the position and structure of such domains and thus may influence protein function. Conversely, the bilayer itself can (locally) change the thickness of its hydrocarbon region to interact optimally with hydrophobic regions of a transmembrane protein (a.k.a. hydrophobic matching). WALPs provide an effective model for studying such interactions because of their systematic design of a core of hydrophobic, alternating alanine and leucine regions.[2] This core is readily manipulated by extending or decreasing the number of amino acids. Another key feature is the presence of "anchoring" residues at the ends of the helix, which are tryptophan residues in the WALP versions. Substituting the anchoring tryptophan residues for charged residues, such as lysine, yields "KALP" peptides.[3] This class of model peptides has proved useful for studying the impact of changes in lipid composition on peptide insertion. Following detailed experimental studies by various techniques, the WALP and related peptides have become commonly used model systems in computational biology.
Responses to lipid environmentedit
When hydrophobic mismatch occurs, WALPs are known to tilt in the bilayer.[4] The extent of this tilt is affected up to a certain point by an entropy contribution that arises from the helix's presence in the bilayer and then by more specific helix-lipid interactions. When charged residues are substituted for the anchoring residues, these charged amino acids prefer a higher position, farther from the interior of the lipid bilayer, in order to maintain their energetically favorable interaction with water. This interaction thus promotes a smaller angle of tilt.
Referencesedit
Siegel, David P.; Cherezov, V.; Greathouse, D. V.; Koeppe, R. E.; Antoinette Killian, J.; Caffrey, M. (January 2006). "Transmembrane Peptides Stabilize Inverted Cubic Phases in a Biphasic Length-Dependent Manner: Implications for Protein-Induced Membrane Fusion". Biophysical Journal. 90 (1). Biophysical Society: 200–211. Bibcode:2006BpJ....90..200S. doi:10.1529/biophysj.105.070466. PMC1367019. PMID 16214859.
Weiss, Thomas M.; Van der Wel, Patrick C.A.; Antoinette Killian, J.; Koeppe, II, Roger E.; Huang, Huey W. (January 2003). "Hydrophobic Mismatch between Helices and Lipid Bilayers". Biophysical Journal. 84 (1). Biophysical Society: 379–385. Bibcode:2003BpJ....84..379W. doi:10.1016/S0006-3495(03)74858-9. PMC1302619. PMID 12524291.
Kim, Taehoon; Im, Wonpil (July 2010). "Revisiting Hydrophobic Mismatch with Free Energy Simulation Studies of Transmembrane Helix Tilt and Rotation". Biophysical Journal. 99 (6). Biophysical Society: 175–183. Bibcode:2010BpJ....99..175K. doi:10.1016/j.bpj.2010.04.015. PMC2895360. PMID 20655845.
^Killian, J.Antoinette (2003). "Synthetic peptides as models for intrinsic membrane proteins". FEBS Letters. 555 (1): 134–138. doi:10.1016/S0014-5793(03)01154-2. PMID 14630333.
^Killian, J. Antoinette; Salemink, Irene; de Planque, Maurits R. R.; Lindblom, Göran; Koeppe, Roger E.; Greathouse, Denise V. (1 January 1996). "Induction of Nonbilayer Structures in Diacylphosphatidylcholine Model Membranes by Transmembrane α-Helical Peptides: Importance of Hydrophobic Mismatch and Proposed Role of Tryptophans". Biochemistry. 35 (3): 1037–1045. doi:10.1021/bi9519258.
^de Planque, Maurits R.R.; Kruijtzer, John A.W.; Liskamp, Rob M.J.; Marsh, Derek; Greathouse, Denise V.; Koeppe, Roger E.; de Kruijff, Ben; Killian, J. Antoinette (July 1999). "Different Membrane Anchoring Positions of Tryptophan and Lysine in Synthetic Transmembrane α-Helical Peptides". Journal of Biological Chemistry. 274 (30): 20839–20846. doi:10.1074/jbc.274.30.20839. hdl:11858/00-001M-0000-0012-FA62-5.
^Weiss, Thomas M.; van der Wel, Patrick C.A.; Killian, J. Antoinette; Koeppe, Roger E.; Huang, Huey W. (January 2003). "Hydrophobic Mismatch between Helices and Lipid Bilayers". Biophysical Journal. 84 (1): 379–385. doi:10.1016/S0006-3495(03)74858-9. PMC1302619.
May 04, 2024
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This article includes a list of general references but it lacks sufficient corresponding inline citations Please help to improve this article by introducing more precise citations March 2011 Learn how and when to remove this message WALP peptides are a class of synthesized membrane spanning a helices composed of tryptophan W alanine A and leucine L amino acids They are designed to study properties of proteins in lipid membranes such as orientation extent of insertion and hydrophobic mismatch 1 WALP 19 protein peptide of the following sequence of 19 amino acids GWWLALALALALALALWWA Tryptophan residues are shown in green while leucines and alanines are displayed in red and blue respectively Significance editThe transmembrane region of many integral membrane proteins consists of one or more alpha helices The orientations and interactions of these helices directly affect cell signaling and molecular transport across the bilayer The hydrophobic environment of the phospholipid tails in turn modulates the position and structure of such domains and thus may influence protein function Conversely the bilayer itself can locally change the thickness of its hydrocarbon region to interact optimally with hydrophobic regions of a transmembrane protein a k a hydrophobic matching WALPs provide an effective model for studying such interactions because of their systematic design of a core of hydrophobic alternating alanine and leucine regions 2 This core is readily manipulated by extending or decreasing the number of amino acids Another key feature is the presence of anchoring residues at the ends of the helix which are tryptophan residues in the WALP versions Substituting the anchoring tryptophan residues for charged residues such as lysine yields KALP peptides 3 This class of model peptides has proved useful for studying the impact of changes in lipid composition on peptide insertion Following detailed experimental studies by various techniques the WALP and related peptides have become commonly used model systems in computational biology Responses to lipid environment editWhen hydrophobic mismatch occurs WALPs are known to tilt in the bilayer 4 The extent of this tilt is affected up to a certain point by an entropy contribution that arises from the helix s presence in the bilayer and then by more specific helix lipid interactions When charged residues are substituted for the anchoring residues these charged amino acids prefer a higher position farther from the interior of the lipid bilayer in order to maintain their energetically favorable interaction with water This interaction thus promotes a smaller angle of tilt References editSiegel David P Cherezov V Greathouse D V Koeppe R E Antoinette Killian J Caffrey M January 2006 Transmembrane Peptides Stabilize Inverted Cubic Phases in a Biphasic Length Dependent Manner Implications for Protein Induced Membrane Fusion Biophysical Journal 90 1 Biophysical Society 200 211 Bibcode 2006BpJ 90 200S doi 10 1529 biophysj 105 070466 PMC 1367019 PMID 16214859 Weiss Thomas M Van der Wel Patrick C A Antoinette Killian J Koeppe II Roger E Huang Huey W January 2003 Hydrophobic Mismatch between Helices and Lipid Bilayers Biophysical Journal 84 1 Biophysical Society 379 385 Bibcode 2003BpJ 84 379W doi 10 1016 S0006 3495 03 74858 9 PMC 1302619 PMID 12524291 Kim Taehoon Im Wonpil July 2010 Revisiting Hydrophobic Mismatch with Free Energy Simulation Studies of Transmembrane Helix Tilt and Rotation Biophysical Journal 99 6 Biophysical Society 175 183 Bibcode 2010BpJ 99 175K doi 10 1016 j bpj 2010 04 015 PMC 2895360 PMID 20655845 Killian J Antoinette 2003 Synthetic peptides as models for intrinsic membrane proteins FEBS Letters 555 1 134 138 doi 10 1016 S0014 5793 03 01154 2 PMID 14630333 Killian J Antoinette Salemink Irene de Planque Maurits R R Lindblom Goran Koeppe Roger E Greathouse Denise V 1 January 1996 Induction of Nonbilayer Structures in Diacylphosphatidylcholine Model Membranes by Transmembrane a Helical Peptides Importance of Hydrophobic Mismatch and Proposed Role of Tryptophans Biochemistry 35 3 1037 1045 doi 10 1021 bi9519258 de Planque Maurits R R Kruijtzer John A W Liskamp Rob M J Marsh Derek Greathouse Denise V Koeppe Roger E de Kruijff Ben Killian J Antoinette July 1999 Different Membrane Anchoring Positions of Tryptophan and Lysine in Synthetic Transmembrane a Helical Peptides Journal of Biological Chemistry 274 30 20839 20846 doi 10 1074 jbc 274 30 20839 hdl 11858 00 001M 0000 0012 FA62 5 Weiss Thomas M van der Wel Patrick C A Killian J Antoinette Koeppe Roger E Huang Huey W January 2003 Hydrophobic Mismatch between Helices and Lipid Bilayers Biophysical Journal 84 1 379 385 doi 10 1016 S0006 3495 03 74858 9 PMC 1302619 Retrieved from https en wikipedia org w index php title WALP peptide amp oldid 1187462495, wikipedia, wiki, book, books, library,
