主讲人：F. Tian教授

主持人：赵欣 教授

开始时间：2012-10-08 14:00

讲座地址：中北校区理科大楼A510报告厅

主办单位：物理系和科技处

报告人简介：

F. Tian为美国宾夕法尼亚州立大学医学院核磁中心主任。2011 – Director of NMR core facility,  College of Medicine, the Pennsylvania State University ；2008 –Assistant  Professor, Department of Biochemistry and Molecular Biology, College of  Medicine, the Pennsylvania State University； 2005 – 2008Assistant  Research Scientist, Collaboration Coordinator for NMR method group,  Southeast Collaboratory for Biomolecular NMR, the University of  Georgia；2003 – 2005 Senior Chemist, Eli Lilly and Corporation；2001 –  2003 Senior Research Scientist, Pharmacia/Pfizer Corporation； 2000 –  2001 Project Coordinator, Southeast Collaboratory for Structural  Genomics, the University of Georgia.

报告内容简介：

Biological membranes adopt diverse and dynamic geometries. For  example, bacteria display a wide range of shapes, ranging from spheres  to rods and spirals; the internal membranes of eukaryotic cells are  stunning arrays of tubules, sheets, vesicles, and cisternae.Many  essential cellular processes such as endocytosis, vesiculation,  organelle synthesis and cell division require transient membrane  deformations, and the activity of some proteins (e.g. human ArfGAP1)  dramatically increases with the curvature of the membrane bilayer.

Recently, it was discovered that membrane curvature could serve as a  geometric cue for the subcellular localization of some proteins (e. g.  SpoVM and DivIVA).Membrane geometry is increasingly viewed as a critical  component for creating microenvironments for membrane fusion and  fission, protein localization, trafficking and signaling.This  underscores the importance of understanding the molecular mechanisms  responsible for the generation, recognition, maintenance, and regulation  of membrane architecture. SpoVM, a 26-residue peptide, was recently  found to recognize and preferentially localize to the slightly curved  outer surface of the forespore (diameter of curvature, R, ~1 µm) during  Bacillus subtilis spore development.However, little is known about how  this is accomplished.

SpoVM was predicted to exist as a straight, amphipathic α-helix that  shallowly inserts into the membrane surface.However, using solution NMR,  we have found that the SpoVM molecule adopts a loop-helix structure and  that the helix deeply embedded into bicelles.This model has provided  new structural insights into SpoVM function.We are extending this study  with model membranes that are similar in curvature and lipid composition  to that of the B. subtilis forespore using solid-state NMR.

LR11 (sorLA) is a type I membrane protein that mediates the  trans-Golgi network to endosome sorting of multiple growth factors.LR11  is a central player in the amyloidogenic processing of the amyloid  precursor protein that is implicated in development of Alzheimer’s  disease.We discovered that an amphipathic α-helix in LR11 C-terminal  domain deforms the membrane and shares characteristic features of the  motif that senses highly curved membranes (R, ~50 nm).Since changes in  membrane curvature are inherent to trafficking events, we are  investigating how this helix senses and/or induces the bending of the  membrane to facilitate intracellular transport.We are also pursuing its  atomic structure in a native membrane using the in situ (ex vivo)  solid-state NMR spectroscopy.