NMR of Membrane-Associated Peptides and Proteins

Wang, Guangshun

doi:10.2174/138920308783565714

Cited by 58 publications

(33 citation statements)

References 172 publications

(360 reference statements)

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“…Membrane-mimetic models are normally utilized to determine the membrane-bound structures of receptors or AMPs. These models include organic solvents, detergent/lipid micelles, lipid bicelles, nanodiscs, and lipid bilayers [198,199]. The known 3D structures of these short peptides are primarily determined by multi-dimensional solution nuclear magnetic resonance (NMR) spectroscopy [199].…”

Section: Three-dimensional Structures Of Human Antimicrobial Peptidesmentioning

confidence: 99%

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Human Antimicrobial Peptides and Proteins

2014

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As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to combat drug-resistant superbugs, fungi, viruses, parasites, or cancer. Alternatively, multiple factors (e.g., albumin, arginine, butyrate, calcium, cyclic AMP, isoleucine, short-chain fatty acids, UV B light, vitamin D, and zinc) are able to induce the expression of antimicrobial peptides, opening new avenues to the development of anti-infectious drugs.

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Section: Three-dimensional Structures Of Human Antimicrobial Peptidesmentioning

confidence: 99%

“…For example, the oligomeric structure of a K + channel did not survive in TFE but retained in membrane-mimetic micelles such as SDS (reviewed in ref. [198]). These examples emphasize the importance of determining the 3D structure of AMPs in a proper environment.…”

Section: Three-dimensional Structures Of Human Antimicrobial Peptidesmentioning

confidence: 99%

Human Antimicrobial Peptides and Proteins

2014

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“…Solution and solid state NMR is starting to make a significant dent, however, and it appears that GPCR-sized proteins may become accessible to these techniques. [67][68][69] For both crystallography and NMR, the key elements that can pave the way to a structure are high-level expression, protein stability, and conformational homogeneity. New methods that can attack these fundamental issues more reliably, more generally and with greater ease of implementation will continue to build the membrane protein structure revolution.…”

Section: Resultsmentioning

confidence: 99%

G‐protein‐coupled receptor structures were not built in a day

Blois

Bowie

2009

Protein Science

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Among the most exciting recent developments in structural biology is the structure determination of G-protein-coupled receptors (GPCRs), which comprise the largest class of membrane proteins in mammalian cells and have enormous importance for disease and drug development. The GPCR structures are perhaps the most visible examples of a nascent revolution in membrane protein structure determination. Like other major milestones in science, however, such as the sequencing of the human genome, these achievements were built on a hidden foundation of technological developments. Here, we describe some of the methods that are fueling the membrane protein structure revolution and have enabled the determination of the current GPCR structures, along with new techniques that may lead to future structures.

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“…For example, apoC-II can bind specifi c phospholipids within lipid membranes, and thereby locally remodel the composition of the lipid surface (Hanson et al 2003 ). Conversely, lipid surfaces have a significant effect on apoC-II structure; binding of lipid surfaces almost always results in the stabilisation of a native α-helical structure in this (MacRaild et al , 2004 ) and other apolipoproteins [for review see (Wang 2008 )]. However, there is evidence that apoC-II can adopt an amyloid structure in atherosclerotic plaques, which are highly enriched in a range of modifi ed lipids (Medeiros et al 2004 ;Teoh et al 2011a ).…”

Section: The Structure Of Apoc-ii Bound To Lipid Micellesmentioning

confidence: 99%

The Role of Lipid in Misfolding and Amyloid Fibril Formation by Apolipoprotein C-II

Ryan

Mok

Howlett

et al. 2015

Advances in Experimental Medicine and Biology

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Apolipoproteins are a key component of lipid transport in the circulatory system and share a number of structural features that facilitate this role. When bound to lipoprotein particles, these proteins are relatively stable. However, in the absence of lipids they display conformational instability and a propensity to aggregate into amyloid fibrils. Apolipoprotein C-II (apoC-II) is a member of the apolipoprotein family that has been well characterised in terms of its misfolding and aggregation. In the absence of lipid, and at physiological ionic strength and pH, apoC-II readily forms amyloid fibrils with a twisted ribbon-like morphology that are amenable to a range of biophysical and structural analyses. Consistent with its lipid binding function, the misfolding and aggregation of apoC-II are substantially affected by the presence of lipid. Short-chain phospholipids at submicellar concentrations significantly accelerate amyloid formation by inducing a tetrameric form of apoC-II that can nucleate fibril aggregation. Conversely, phospholipid micelles and bilayers inhibit the formation of apoC-II ribbon-type fibrils, but induce slow formation of amyloid with a distinct straight fibril morphology. Our studies of the effects of lipid at each stage of amyloid formation, detailed in this chapter, have revealed complex behaviour dependent on the chemical nature of the lipid molecule, its association state, and the protein:lipid ratio.

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NMR of Membrane-Associated Peptides and Proteins

Cited by 58 publications

References 172 publications

Human Antimicrobial Peptides and Proteins

Human Antimicrobial Peptides and Proteins

G‐protein‐coupled receptor structures were not built in a day

The Role of Lipid in Misfolding and Amyloid Fibril Formation by Apolipoprotein C-II

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