Editing Peripheral membrane protein (section)

==Spatial position in membrane==
Orientations and penetration depths of many amphitropic proteins and peptides in membranes are studied using [[site-directed spin labeling]],<ref name="Malmberg">{{cite journal | vauthors = Malmberg NJ, Falke JJ | title = Use of EPR power saturation to analyze the membrane-docking geometries of peripheral proteins: applications to C2 domains | journal = Annual Review of Biophysics and Biomolecular Structure | volume = 34 | issue = 1 | pages = 71–90 | year = 2005 | pmid = 15869384 | pmc = 3637887 | doi = 10.1146/annurev.biophys.34.040204.144534 }}</ref> chemical labeling, measurement of membrane binding affinities of protein [[mutagenesis|mutants]],<ref name="Spencer">{{cite journal | vauthors = Spencer AG, Thuresson E, Otto JC, Song I, Smith T, DeWitt DL, Garavito RM, Smith WL | display-authors = 6 | title = The membrane binding domains of prostaglandin endoperoxide H synthases 1 and 2. Peptide mapping and mutational analysis | journal = The Journal of Biological Chemistry | volume = 274 | issue = 46 | pages = 32936–32942 | date = November 1999 | pmid = 10551860 | doi = 10.1074/jbc.274.46.32936 | doi-access = free }}</ref> [[fluorescence]] spectroscopy,<ref name="Lathrop">{{cite journal | vauthors = Lathrop B, Gadd M, Biltonen RL, Rule GS | title = Changes in Ca2+ affinity upon activation of Agkistrodon piscivorus piscivorus phospholipase A2 | journal = Biochemistry | volume = 40 | issue = 11 | pages = 3264–3272 | date = March 2001 | pmid = 11258945 | doi = 10.1021/bi001901n }}</ref> solution or solid-state [[NMR spectroscopy]],<ref name="Kuta">{{cite journal | vauthors = Kutateladze T, Overduin M | title = Structural mechanism of endosome docking by the FYVE domain | journal = Science | volume = 291 | issue = 5509 | pages = 1793–1796 | date = March 2001 | pmid = 11230696 | doi = 10.1126/science.291.5509.1793 | bibcode = 2001Sci...291.1793K }}</ref>
ATR [[Fourier transform spectroscopy|FTIR spectroscopy]],<ref name="Tatulian">{{cite journal | vauthors = Tatulian SA, Qin S, Pande AH, He X | title = Positioning membrane proteins by novel protein engineering and biophysical approaches | journal = Journal of Molecular Biology | volume = 351 | issue = 5 | pages = 939–947 | date = September 2005 | pmid = 16055150 | doi = 10.1016/j.jmb.2005.06.080 | url = https://zenodo.org/record/894918 }}</ref> X-ray or neutron diffraction,<ref name="Hristova"/> and computational methods.<ref name="Murray">{{cite journal | vauthors = Murray D, Honig B | title = Electrostatic control of the membrane targeting of C2 domains | journal = Molecular Cell | volume = 9 | issue = 1 | pages = 145–154 | date = January 2002 | pmid = 11804593 | doi = 10.1016/S1097-2765(01)00426-9 | doi-access = free }}</ref><ref name="Efremov">{{cite journal | vauthors = Efremov RG, Nolde DE, Konshina AG, Syrtcev NP, Arseniev AS | title = Peptides and proteins in membranes: what can we learn via computer simulations? | journal = Current Medicinal Chemistry | volume = 11 | issue = 18 | pages = 2421–2442 | date = September 2004 | pmid = 15379706 | doi = 10.2174/0929867043364496 }}</ref><ref name="Lomize">{{cite journal | vauthors = Lomize AL, Pogozheva ID, Lomize MA, Mosberg HI | title = Positioning of proteins in membranes: a computational approach | journal = Protein Science | volume = 15 | issue = 6 | pages = 1318–1333 | date = June 2006 | pmid = 16731967 | pmc = 2242528 | doi = 10.1110/ps.062126106 }}</ref><ref>{{cite web|vauthors=Lomize A, Lomize M, Pogozheva I |title=Comparison with experimental data | work=Orientations of Proteins in Membranes |publisher=University of Michigan |url=http://opm.phar.umich.edu/about.php?subject=experiments |access-date=2007-02-08}}</ref>

Two distinct membrane-association modes of proteins have been identified. Typical water-soluble proteins have no exposed nonpolar residues or any other hydrophobic anchors. Therefore, they remain completely in aqueous solution and do not penetrate into the lipid bilayer, which would be energetically costly. Such proteins interact with bilayers only electrostatically, for example, [[ribonuclease]] and [[poly-lysine]] interact with membranes in this mode. However, typical amphitropic proteins have various hydrophobic anchors that penetrate the interfacial region and reach the hydrocarbon interior of the membrane. Such proteins "deform" the lipid bilayer, decreasing the temperature of lipid fluid-gel transition.<ref name=Papahadjopoulos_1975>{{cite journal | vauthors = Papahadjopoulos D, Moscarello M, Eylar EH, Isac T | title = Effects of proteins on thermotropic phase transitions of phospholipid membranes | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 401 | issue = 3 | pages = 317–335 | date = September 1975 | pmid = 52374 | doi = 10.1016/0005-2736(75)90233-3 }}</ref> The binding is usually a strongly exothermic reaction.<ref name=Seelig_2004>{{cite journal | vauthors = Seelig J | title = Thermodynamics of lipid-peptide interactions | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 1666 | issue = 1–2 | pages = 40–50 | date = November 2004 | pmid = 15519307 | doi = 10.1016/j.bbamem.2004.08.004 | doi-access = free }}</ref> Association of amphiphilic α-helices with membranes occurs similarly.<ref name="Hristova">{{cite journal | vauthors = Hristova K, Wimley WC, Mishra VK, Anantharamiah GM, Segrest JP, White SH | title = An amphipathic alpha-helix at a membrane interface: a structural study using a novel X-ray diffraction method | journal = Journal of Molecular Biology | volume = 290 | issue = 1 | pages = 99–117 | date = July 1999 | pmid = 10388560 | doi = 10.1006/jmbi.1999.2840 }}</ref><ref name="Darkes">{{cite journal |vauthors=Darkes MJ, Davies SM, Bradshaw JP |title=Interaction of tachykinins with phospholipid membranes: A neutron diffraction study |journal=Physica B |year=1997 |volume=241 |pages=1144–1147 |bibcode=1997PhyB..241.1144D |doi=10.1016/S0921-4526(97)00811-9}}</ref> [[Intrinsically unstructured proteins|Intrinsically unstructured]] or [[Denaturation (biochemistry)|unfolded]] peptides with nonpolar residues or lipid anchors can also penetrate the interfacial region of the membrane and reach the hydrocarbon core, especially when such peptides are cationic and interact with negatively charged membranes.<ref name="Ellena">{{cite journal | vauthors = Ellena JF, Moulthrop J, Wu J, Rauch M, Jaysinghne S, Castle JD, Cafiso DS | title = Membrane position of a basic aromatic peptide that sequesters phosphatidylinositol 4,5 bisphosphate determined by site-directed spin labeling and high-resolution NMR | journal = Biophysical Journal | volume = 87 | issue = 5 | pages = 3221–3233 | date = November 2004 | pmid = 15315949 | pmc = 1304792 | doi = 10.1529/biophysj.104.046748 | bibcode = 2004BpJ....87.3221E }}</ref><ref name="Marcotte">{{cite journal | vauthors = Marcotte I, Dufourc EJ, Ouellet M, Auger M | title = Interaction of the neuropeptide met-enkephalin with zwitterionic and negatively charged bicelles as viewed by 31P and 2H solid-state NMR | journal = Biophysical Journal | volume = 85 | issue = 1 | pages = 328–339 | date = July 2003 | pmid = 12829487 | pmc = 1303088 | doi = 10.1016/S0006-3495(03)74477-4 | bibcode = 2003BpJ....85..328M }}</ref><ref name="Zhang">{{cite journal | vauthors = Zhang W, Crocker E, McLaughlin S, Smith SO | title = Binding of peptides with basic and aromatic residues to bilayer membranes: phenylalanine in the myristoylated alanine-rich C kinase substrate effector domain penetrates into the hydrophobic core of the bilayer | journal = The Journal of Biological Chemistry | volume = 278 | issue = 24 | pages = 21459–21466 | date = June 2003 | pmid = 12670959 | doi = 10.1074/jbc.M301652200 | doi-access = free }}</ref>