https://minerva-access.unimelb.edu.au/bitstream/handle/11343/194901/Stockwell_Cell_review+2017.pdf

Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease

Small GTP-binding proteins (G proteins) exist in eukaryotes from yeast to human and constitute a superfamily consisting of more than 100 members. This superfamily is structurally classified into at least five families: the Ras, Rho, Rab, Sar1/Arf, and Ran families. They regulate a wide variety of cell functions as biological timers (biotimers) that initiate and terminate specific cell functions and determine the periods of time for the continuation of the specific cell functions. They furthermore play key roles in not only temporal but also spatial determination of specific cell functions. The Ras family regulates gene expression, the Rho family regulates cytoskeletal reorganization and gene expression, the Rab and Sar1/Arf families regulate vesicle trafficking, and the Ran family regulates nucleocytoplasmic transport and microtubule organization. Many upstream regulators and downstream effectors of small G proteins have been isolated, and their modes of activation and action have gradually been elucidated. Cascades and cross-talks of small G proteins have also been clarified. In this review, functions of small G proteins and their modes of activation and action are described.

Small GTP-Binding Proteins

The process by which extracellular signals are relayed from the plasma membrane to specific intracellular sites is an essential facet of cellular regulation. Many signaling pathways do so by altering the phosphorylation state of tyrosine, serine, or threonine residues of target proteins. Recently, it has become apparent that regulatory mechanisms exist to influence where and when protein kinases and phosphatases are activated in the cell. The role of scaffold, anchoring, and adaptor proteins that contribute to the specificity of signal transduction events by recruiting active enzymes into signaling networks or by placing enzymes close to their substrates is discussed.

https://faculty.washington.edu/scottjdw/pdfs/pawson_sci_1997_p2075.pdf

Signaling Through Scaffold, Anchoring, and Adaptor Proteins

Membrane curvature is no longer seen as a passive consequence of cellular activity but an active means to create membrane domains and to organize centres for membrane trafficking. Curvature can be dynamically modulated by changes in lipid composition, the oligomerization of curvature scaffolding proteins and the reversible insertion of protein regions that act like wedges in membranes. There is an interplay between curvature-generating and curvature-sensing proteins during vesicle budding. This is seen during vesicle budding and in the formation of microenvironments. On a larger scale, membrane curvature is a prime player in growth, division and movement.

/pdf/membrane-curvature-and-mechanisms-of-dynamic-cell-membrane-2hm38oqsgo.pdf

Membrane curvature and mechanisms of dynamic cell membrane remodelling

Somlyo, Andrew P., and Avril V. Somlyo. Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase. Physiol Rev 83: 1325-1358, 2003; 10.1152...

https://www.physiology.org/doi/pdf/10.1152/physrev.00023.2003

Ca2+ Sensitivity of Smooth Muscle and Nonmuscle Myosin II: Modulated by G Proteins, Kinases, and Myosin Phosphatase

Summary: HELIQUEST calculates the physicochemical properties and amino acid composition of an α-helix and screens databank to identify protein segments possessing similar features. This server is also dedicated to mutating helices manually or automatically by genetic algorithm to design analogues of defined features. Availability: http://heliquest.ipmc.cnrs.fr

/pdf/heliquest-a-web-server-to-screen-sequences-with-specific-a-9kg8ha6ckc.pdf

HELIQUEST: a web server to screen sequences with specific α-helical properties

A Four-Step Cycle Driven by PI(4)P Hydrolysis Directs Sterol/PI(4)P Exchange by the ER-Golgi Tether OSBP

The Golgi-associated protein ArfGAP1 has an unusual membrane-adsorbing amphipathic α-helix: its polar face is weakly charged, containing mainly serine and threonine residues. We show that this feature explains the specificity of ArfGAP1 for curved versus flat lipid membranes. We built an algorithm to identify other potential amphipathic α-helices rich in serine and threonine residues in protein databases. Among the identified sequences, we show that three act as membrane curvature sensors. In the golgin GMAP-210, the sensor may serve to trap small vesicles at the end of a long coiled coil. In Osh4p/Kes1p, which transports sterol between membranes, the sensor controls access to the sterol-binding pocket. In the nucleoporin Nup133, the sensor corresponds to an exposed loop of a β-propeller structure. Ser/Thr-rich amphipathic helices thus define a general motif used by proteins of various functions for sensing membrane curvature.

A general amphipathic |[alpha]|-helical motif for sensing membrane curvature

https://febs.onlinelibrary.wiley.com/doi/epdf/10.1016/j.febslet.2009.10.022

Amphipathic helices and membrane curvature

THE small G protein ARF1 is involved in the coating of vesicles that bud from the Golgi compartments1,2. Its activation is controlled by as-yet unidentified guanine-nucleotide exchange factors3,4. Geal, the first ART exchange factor to be discovered in yeast5, is a large protein containing a domain of homology with Sec7, another yeast protein that is also involved in secretion6. Here we characterized a smaller human protein (relative molecular mass 47K) named ARNO, which contains a central Sec7 domain that promotes guanine-nucleotide exchange on ARF1. ARNO also contains an amino-terminal coiled-coil motif and a carboxy-terminal pleckstrin-homology (PH) domain. The PH domain mediates an enhancement of ARNO exchange activity by negatively charged phospholipid vesicles supplemented with phosphatidylinositol bisphosphate. The exchange activity of ARNO is not inhibited by brefeldin A, an agent known to block vesicular transport and inhibit the exchange activity on ARF1 in cell extracts7,8. This suggests that a regulatory component which is sensitive to brefeldin A associates with ARNO in vivo, possibly through the amino-terminal coiled-coil. We propose that other proteins with a Sec7 domain regulate different members of the ART family.

Bruno Antonny

Papers

HELIQUEST: a web server to screen sequences with specific α-helical properties

A Four-Step Cycle Driven by PI(4)P Hydrolysis Directs Sterol/PI(4)P Exchange by the ER-Golgi Tether OSBP

A general amphipathic |[alpha]|-helical motif for sensing membrane curvature

Amphipathic helices and membrane curvature

A human exchange factor for ARF contains Sec7- and pleckstrin-homology domains.