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TitleA PH domain in ACAP1 possesses key features of the BAR domain in promoting membrane curvature.
Journal, issue, pagesDev Cell, Vol. 31, Issue 1, Page 73-86, Year 2014
Publish dateOct 13, 2014
AuthorsXiaoyun Pang / Jun Fan / Yan Zhang / Kai Zhang / Bingquan Gao / Jun Ma / Jian Li / Yuchen Deng / Qiangjun Zhou / Edward H Egelman / Victor W Hsu / Fei Sun /
PubMed AbstractThe BAR (Bin-Amphiphysin-Rvs) domain undergoes dimerization to produce a curved protein structure, which superimposes onto membrane through electrostatic interactions to sense and impart membrane ...The BAR (Bin-Amphiphysin-Rvs) domain undergoes dimerization to produce a curved protein structure, which superimposes onto membrane through electrostatic interactions to sense and impart membrane curvature. In some cases, a BAR domain also possesses an amphipathic helix that inserts into the membrane to induce curvature. ACAP1 (Arfgap with Coil coil, Ankyrin repeat, and PH domain protein 1) contains a BAR domain. Here, we show that this BAR domain can neither bind membrane nor impart curvature, but instead requires a neighboring PH (Pleckstrin Homology) domain to achieve these functions. Specific residues within the PH domain are responsible for both membrane binding and curvature generation. The BAR domain adjacent to the PH domain instead interacts with the BAR domains of neighboring ACAP1 proteins to enable clustering at the membrane. Thus, we have uncovered the molecular basis for an unexpected and unconventional collaboration between PH and BAR domains in membrane bending.
External linksDev Cell / PubMed:25284369 / PubMed Central
MethodsEM (helical sym.) / X-ray diffraction
Resolution2.2 - 17.0 Å
Structure data

2546

4ckg

EMDB-2546, PDB-4ckg:
Helical reconstruction of ACAP1(BAR-PH domain) decorated membrane tubules by cryo-electron microscopy
Method: EM (helical sym.) / Resolution: 15.0 Å

2547

4ckh

EMDB-2547, PDB-4ckh:
Helical reconstruction of ACAP1(BAR-PH domain) decorated membrane tubules by cryo-electron microscopy
Method: EM (helical sym.) / Resolution: 17.0 Å

PDB-4nsw:
Crystal structure of the BAR-PH domain of ACAP1
Method: X-RAY DIFFRACTION / Resolution: 2.2 Å

Chemicals

ChemComp-HOH:
WATER / Water

Source
  • homo sapiens (human)
KeywordsSIGNALING PROTEIN / MEMBRANE REMODELING / PROTEIN TRANSPORT / COILED-COIL / BAR DOMAIN / PH DOMAIN / GTPASE ACTIVATION

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